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Background: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period., Methods: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium., Results: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure., Conclusion: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Sheffield NARCOS (National Adverse Reactions Advisory Service) investigates suspected perioperative anaesthetic reactions using serial tryptase, urinary methylhistamine (UMH) and clinical information. Further recommendations for additional allergy clinic assessment are provided., Objective: To establish a robustly measurable protocol for identifying mast cell mediator (MMR) release in this cohort. To compare these thresholds with previously suggested thresholds and algorithms., Method: A review of 3455 NARCOS cases referred with a suspected perioperative allergic reaction. Tryptase, UMH and clinical details were analysed. A total of 1746 cases were graded using the Ring and Messmer scale. Reaction grade, tryptase and UMH changes were compared with statistical and graphical presentations appropriate to non-normally distributed measurements using Analyse-IT software., Results: Sensitive strategies such as 3 μg/L or 20% are measurable and translatable and would substantially increase detection of potentially relevant changes in tryptases. Adequate quality assurance for low-level measurement is needed. An incremental threshold of 20% would identify potential MMR in an additional 14% of cases with peak tryptase (Tp) between 5 and 14 μg/L and a further 15% with Tp below 5 μg/L. Further work is required to establish the diagnostic performance characteristics of this more sensitive approach. UMH also identified up to 120 further cases of potential MMR in the absence of tryptase increments., Conclusions and Clinical Relevance: Future studies should establish and compare the predictive performance characteristics of each strategy against clinical phenotypes. A single agreed definition of positive serial tryptases is needed to enable robust evaluation of diagnostic strategies. This could serve as a harmonized standard for comparative studies of case series from different centres., (© 2016 John Wiley & Sons Ltd.)

Background: Recent epidemiological studies indicate increases in Australian, UK and US hospital anaphylaxis admission rates., Objectives: The aim of this study was to determine whether Australian anaphylaxis fatalities are increasing in parallel and to examine the characteristics of fatalities recorded in the National Coronial Information System (NCIS)., Methods: Time trends in Australian anaphylaxis fatalities were examined using data derived from the Australian Bureau of Statistics (ABS) 1997-2013 and the NCIS 2000-2013, the latter providing additional information to verify cause and identify risk factors., Results: The ABS recorded 324 anaphylaxis fatalities by cause: unspecified (n = 205); medication (n = 52); insect stings/tick bites (n = 41); food (n = 23); and blood products (n = 3). From 1997 to 2013, all-cause fatal anaphylaxis rates increased by 6.2%/year (95% CI: 3.8-8.6%, P < 0.0001) or from 0.054% to 0.099/10(5) population. Fatal food anaphylaxis increased by 9.7%/year (95% CI: 0.25-20%, P = 0.04) and unspecified anaphylaxis deaths by 7.8% (95% CI: 4.6-11.0, P < 0.0001). There was an insignificant change in medication-related fatalities (5.6% increase/year; 95% CI: 0.3% decrease to 11.8% increase, P = 0.06), and sting/bite fatalities remained unchanged. Hospital anaphylaxis admission rates for all-cause, food, unspecified and medication anaphylaxis increased at rates of 8%, 10%, 4.4% and 6.8%/year, respectively. A total of 147 verified NCIS deaths were examined in detail: medication- and sting/bite-related fatalities occurred predominantly in older individuals with multiple comorbidities. Upright posture after anaphylaxis was associated with risk of sudden death (all causes). Seafood (not nuts) was the most common trigger for food-related anaphylaxis deaths., Conclusions: Australian anaphylaxis fatality rates (most causes) have increased over the last 16 years, contrasting with UK- and US-based studies that describe overall lower and static overall anaphylaxis fatality rates (0.047-0.069/10(5) population)., (© 2016 John Wiley & Sons Ltd.)

We report on trends in anaphylaxis admissions in the Spanish hospital system during the period 1998-2011. Data on admissions for anaphylaxis were obtained from the Spanish Information System for Hospital Data for the period 1998-2011. Patients were selected using the codes for anaphylaxis in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Poisson regression models were used to estimate incidence rate ratios. We recorded a 1.89-fold increase in admissions for anaphylaxis in Spanish hospitals during the study period, particularly in patients aged 0-14 years (1.65- to 3.22-fold until 2009 and 4.09- to 12.59-fold until 2011) and in food anaphylaxis in all age groups (2.78-fold until 2009 and 8.74-fold until 2011). The incidence of anaphylaxis is perceived as having increased in recent years, especially anaphylaxis caused by food and anaphylaxis affecting the pediatric population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The incidence of anaphylaxis might be increasing. Data for fatal anaphylaxis are limited because of the rarity of this outcome., Objective: We sought to document trends in anaphylaxis admissions and fatalities by age, sex, and cause in England and Wales over a 20-year period., Methods: We extracted data from national databases that record hospital admissions and fatalities caused by anaphylaxis in England and Wales (1992-2012) and crosschecked fatalities against a prospective fatal anaphylaxis registry. We examined time trends and age distribution for fatal anaphylaxis caused by food, drugs, and insect stings., Results: Hospital admissions from all-cause anaphylaxis increased by 615% over the time period studied, but annual fatality rates remained stable at 0.047 cases (95% CI, 0.042-0.052 cases) per 100,000 population. Admission and fatality rates for drug- and insect sting-induced anaphylaxis were highest in the group aged 60 years and older. In contrast, admissions because of food-triggered anaphylaxis were most common in young people, with a marked peak in the incidence of fatal food reactions during the second and third decades of life. These findings are not explained by age-related differences in rates of hospitalization., Conclusions: Hospitalizations for anaphylaxis increased between 1992 and 2012, but the incidence of fatal anaphylaxis did not. This might be due to increasing awareness of the diagnosis, shifting patterns of behavior in patients and health care providers, or both. The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent, which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

There were remarkable achievements in the 19th century in our understanding of the cells of the allergic response, the clear descriptions of hay fever and asthma, as well as the role of pollen in seasonal rhinitis. Although allergy as a concept was not developed until well into the 20th century, the foundations of our present understanding of these diseases were laid in the 1800s. The outstanding physicians and scientists of this time included Paul Ehrlich (who described mast cells, eosinophils and basophils), John Bostock (who provided the first detailed account of hay fever), Charles Blackley (who showed that pollen was the cause of hay fever), Morrill Wyman (who demonstrated that autumnal catarrh was due to ragweed pollen), Henry Hide Salter (who made the first classic description of asthma) and Henri Laënnec (the inventor of the stethoscope)., (© 2014 S. Karger AG, Basel.)

From its very beginning, the 20th century represented the period of the main breakthrough for allergology as a clinical and scientific entity. The first years of this period were extraordinarily exciting because of the discovery of the anaphylactic reaction in 1902 and its clinical diagnosis as 'local anaphylaxis', 'serum sickness' (1903) or even as 'anaphylactic shock' (1907). The term 'allergy' was coined in 1906 and led to the recognition of allergic diseases as a pathogenetic entity. The first patient organization of hay fever sufferers was founded in Germany in 1900, the same year in which the very first report on immunotherapy was published in New York. In 1911 the era of actual immunotherapy started in London, becoming scientific with the first double-blind study in 1956, and still today being regarded as the backbone of allergology. In 1919 it was shown that allergy could be transferred by blood, in 1921 by serum (Prausnitz-Küstner test) and in 1966 the mystic 'reagins' were recognized as immunoglobulin (Ig) E. The development of the radioallergosorbent test for quantifying specific IgE antibody was a diagnostic landmark for allergists all over the world. The history of allergy diagnosis started with the introduction of a 'functional skin test', named the patch test in 1894. The scratch test was described in 1912 and the patch test in 1931. From 1908 the skin was tested by intracutaneous injections, and from 1930 by a 'puncture test' (a precursor of the prick test) which has been in worldwide use in modified variations since 1959. The rub test ('friction test') was added in 1961. Systematically applied provocation tests started with conjunctival provocation (1907), followed by nasal and bronchial provocation with allergens (1914 and 1925)., (© 2014 S. Karger AG, Basel.)

The term anaphylaxis was coined by Charles Richet and Paul Portier when they tried to immunize dogs with actinia extracts, but after a repeated injection of a small amount of the toxin the dog died within 25 min. The new term rapidly spread all over the world. The discovery of the phenomenon of anaphylaxis showed that by immunization not only protection but also harmful events could be induced. For this discovery Richet received the Nobel Prize in 1913, but he still believed the condition of anaphylaxis was a lack of protection to the poisonous effect of the substance. Already earlier similar clinical phenomena had been observed but not well described. A major breakthrough in understanding the pathophysiology came through the experiments of Dale and Laidlaw who showed that the newly discovered histamine was able to induce quite similar symptoms to anaphylaxis. For decades reactions mimicking anaphylaxis but without involvement of the immune systems were called 'anaphylactoid', 'allergy-like' or 'pseudo-allergic'. Since the new definition of the World Allergy Organization (WAO) anaphylaxis is defined on the basis of clinical symptoms independent of pathomechanisms involved: one distinguishes between allergic and non-immune anaphylaxis. Epinephrine (Adrenalin) was soon recognized as treatment of choice of this dramatic condition., (© 2014 S. Karger AG, Basel.)

About 100 years ago, a young paediatrician understood that the function of the immune system should be rationalized not in terms of exemption of disease but in terms of change of reactivity. He coined a new word to represent such an idea: 'allergy': the first contact of the immune system with an antigen changes the reactivity of the individual; on the second and subsequent contacts, this change (or allergy) can induce a spectrum of responses from protective (literally, immune) to hypersensitivity ones. The idea was at first hardly understood by the scientific community because it undermined the essentially protective nature of the immune response as it was defined. Nevertheless, in the next years, the growing clinical evidence led to the acceptance of this new point of view, but not of the new word, at least not unconditionally. The original significance of the neologism 'allergy' became perverted and limited to describe hypersensitivity conditions. Perhaps because of the corruption of the term, today 'allergy' does not have a well-delimited significance among health professionals. Furthermore, the word has long ago escaped from physicians and gone to the streets, where it is popularly used also as synonymous with antipathy and rejection. This vulgarization of the term 'allergy' has significantly increased its imprecision., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The emergence of tetanus in wounded soldiers during the first months of the First World War (WWI) resulted from combat on richly manured fields in Belgium and Northern France, the use of modern explosives that produced deep tissue wounds and the intimate contact between the soldier and the soil upon which he fought. In response, routine prophylactic injections with anti-tetanus serum were given to wounded soldiers removed from the firing line. Subsequently, a steep fall in the incidence of tetanus was observed on both sides of the conflict. Because of fatal serum anaphylaxis associated with administration of serum at a time when purification methods still needed to be improved, it must be presumed that tens to hundreds of men might have died as a result of the routine administration of anti-tetanus serum during WWI. Yet anti-tetanus serum undoubtedly prevented life threatening tetanus among several hundred thousands of wounded men, making it one of the most successful preventive interventions in wartime medicine. After the abrupt fall in tetanus incidence in 1914 due to introduction of anti-tetanus serum, the incidence of the disease tended to become even lower as the war went on. This was probably due to earlier and more thorough surgical treatment, consisting of opening, cleaning, excision and drainage of wounds as early as possible. In this overview, recent battlefield findings from the Meuse-Argonne offensive in 1918 are used to illustrate common practices employed in the prevention of tetanus during WWI.

The discovery of IgE and the role of IgE-mediated inflammation gave clinical allergy a scientific backbone, and as a result, the reputation of the specialty allergy has increased considerably over the years. Allergy diagnosis was improved by assays for in vitro determination of the presence and concentration of IgE antibodies, and clinical knowledge also broadened, allowing better service for the increasing number of allergic individuals. Access to immune assays for allergens finally allowed characterization and standardization of allergen preparations used for diagnosis and allergen-specific immunotherapy. Improved basic molecular technologies have further increased our knowledge about the complex component composition of an allergen extract, introduced IgE-specific immunotherapy, and allowed the allergist to better handle even severe allergic reactions such as anaphylaxis.

Anaphylaxis as the maximal variant of an acute systemic hypersensitivity reaction can involve several organ systems, particularly the skin, respiratory tract, gastrointestinal tract and the cardiovascular system. The severity of anaphylactic reaction is variable and can be classified into severity grades I-IV. Some reactions are fatal. Most frequent elicitors of anaphylaxis are foods in childhood, later insect stings and drugs. The phenomenon itself has been described in ancient medical literature, but was actually recognized and named at the beginning of the 20th century by Charles Richet and Paul Portier. In the course of experiments starting on the yacht of the Prince of Monaco and continued in the laboratory in Paris, they tried to immunize dogs with extracts of Physalia species in an attempt to develop an antitoxin to the venom of the Portuguese man-of-war. While Charles Richet believed that anaphylaxis was a 'lack of protection', it has become clear that an exaggerated immune reaction, especially involving immunoglobulin E antibodies, is the underlying pathomechanism in allergic anaphylaxis besides immune complex reactions. Non-immunologically mediated reactions leading to similar clinical symptomatology have been called 'anaphylactoid' or 'pseudo-allergic'--especially by Paul Kallos--and are now called 'non-immune anaphylaxis' according to a consensus of the World Allergy Organization (WAO). The distinction of different pathophysiological processes is important since non-immune anaphylaxis cannot be detected by skin test or in vitro allergy diagnostic procedures. History and provocation tests are crucial. The intensity of the reaction is not only influenced by the degree of sensitization but also by concomitant other factors as age, simultaneous exposure to other allergens, underlying infection, physical exercise or psychological stress or concomitant medication (e.g. beta-blockers, NSAIDs); this phenomenon has been called augmentation or summation anaphylaxis., (Copyright 2010 S. Karger AG, Basel.)

Cysteinyl leukotrienes are established mediators of bronchial asthma and have agonist roles analogous to those of histamine in allergic rhinitis. We now know that the substance originally termed slow-reacting substance of anaphylaxis was composed of three cysteinyl leukotrienes that act in the inflammatory response via receptors on smooth muscle and on bone marrow-derived inflammatory cells. K. Frank Austen describes the work culminating in the identification, biosynthesis and functional characterization of these moieties.

The pediatrician and scientist, Clemens Freiherr von Pirquet (1874-1929) was the first to coin the term "allergy". His experiments with Behring's serum, which he administered to sick children, led him to an awareness of an interaction between the human organism and pathogens. In his article published in the Müncher Medizinischen Wochenschrift in 1906, he laid the foundation stone for modern allergology.

Summary It is 100 years since Clemens von Pirquet wrote his classic paper introducing the term 'allergy'. Although the word is no longer used in the way he intended, his concept of 'changed reactivity' laid the foundation for the modern science of immunology.

This is a short review on chemical immunosuppression following the discovery of anaphylaxis by Charles Richet. The paper discusses the role of serendipity in the advent of 6-mercapthopurine (6-MP) therapy and the productivity in the field through Nobel Prize recipients.

This article looks at the life of Professor Charles Richet (1850-1935), a distinguished medical scientist who received the Nobel Prize in Physiology or Medicine in 1913 for his work on anaphylaxis. He was also an aeroplane engineer, an investigator of psychic phenomena, active in the medical and international peace movement as a member of the leading peace organisations of the time including the International Medical Association for the Suppression of War, and the French Peace League. He also promoted controversial views about eugenics and the means of constructing what he considered to be a strong and healthy society.

In the inter-war period physicians elaborated numerous 'biotherapies' grounded in the complex interactions between physiology, bacteriology and immunology. The elaboration of these non-specific biological treatments was stimulated by the theory of generalized anaphylaxis that linked the violent reaction to a foreign protein to a broad array of chronic diseases, from asthma and urticaria to rheumatism or chronic colitis. Such diseases were perceived as the result of an 'abnormal reactivity' to a sensitisation of tissues and organs by bacteria and by foreign proteins, a view that provided an effective bridge between new concepts derived from bacteriology and immunology and the long-standing pathological tradition. Accordingly, physicians attempted to treat these conditions through specific desensitisation and non-specific biological therapies: peptone treatment, protein therapy, haemotherapy, 'antivirus' or 'opotherapy'. Therapies that attempted to neutralise the harmful effects of chronic infections through 'desensitisation' were not seen as marginal medical practices, but were promoted by leading advocates of the 'Pasteurian sciences', such as Richet, Widal, Vallery-Radot, Wright and Fleming. They also led to development of new products by the pharmaceutical industry.

Anaphylaxis is the maximal variant of an acute allergic reaction involving several organ systems. The phenomenon itself is old, but it was recognized and named at the beginning of the 20th century by Richet and Portier. The clinical symptoms of anaphylaxis affect various organs, most commonly starting in the skin and proceeding to the respiratory tract, to gastrointestinal involvement and to cardiovascular symptoms, and finally to cardiac and/or respiratory arrest. Anaphylaxis stricto sensu is an immunological reaction, mostly mediated by IgE antibodies, but also by IgG or IgM antibodies (immune complex anaphylaxis). There are cases with similar clinical symptomatology without detectable immunological sensitization which are called pseudo-allergic or anaphylactoid reactions. In the newer nomenclature, some authors tend to include these under the heading of 'anaphylaxis' which has then to be defined as an acute systemic hypersensitivity reaction. The most common elicitors of anaphylaxis include drugs, foods, additives, but also other allergens as well as physical factors (cold, heat, UV radiation). The clinical outcome--the intensity of the reaction--is not only influenced by the degree of sensitization, but also by concomitant other factors: sometimes, individuals only develop anaphylaxis after simultaneous exposure to the allergen and an infection, physical exercise, psychological stress or concomitant medication (e.g. beta blockers). The term 'summation anaphylaxis' has been proposed for this phenomenon which probably underlies many cases of so-called idiopathic anaphylaxis. In patients with insect venom anaphylaxis, decreased levels of plasma angiotensin have been measured in inverse correlation to the severity of the reaction. Certain differential diagnoses have to be distinguished from anaphylaxis. Every patient with a history of anaphylaxis should undergo allergy diagnosis with the aim to detect the eliciting agent, characterize the relevant pathomechanism (e.g. IgE-mediated reaction) and to offer a tolerable alternative (in food or drug allergy). In clear-cut IgE-mediated anaphylaxis, allergen-specific immunotherapy (hyposensitization) is the effective causal treatment, with success rates of 90% in insect venom anaphylaxis.

In 1901, during one of his oceanography cruises, Prince Albert the First of Monaco asks Paul Portier and Charles Richet to study the toxicity of small jellyfish fishing filaments (Coelentera). In the course of their work on the effects of a hypnotoxin extracted from various coelentera, they observe mortal accidents that are not a function of the dosage of the injections. Dogs that respond this way have all received a preparative injection, yet some dogs have no reaction to a second injection. In contrast the injection are activating when they occur more than 10 to 12 days after the first. This phenomenon is independent of the administered dosage, which may well be inferior to a toxic quantity. They call this phenomenon anaphylaxis, the contrary of protection, and analyze its primary characteristics. Paul Portier eventually returns to the Faculty of Sciences where he is Dastre's assistant. Charles Richer pursues research on anaphylaxis on his own in his laboratory at the Medical Faculty. By showing that an immune response could be pathogen as well as healing, these two scientists - who did not know each other before, working together for a few short months - made a discovery that opened up new venues in the growing field of medical immunology.

This text resumes the steps in Immunology that have followed the discovery of anaphylaxis in 1902 by P. Portier and C. Richet. Anaphylaxis was difficult to explain at the beginning of the 20th century where "phylactic" thinking predominated in Immunology. About one hundred years of research were necessary to identify the serum factor, IgE, the cellular actors with their IgE receptors as well as their activation mechanisms and to obtain an atomic view of the interaction between IgE and its receptor. Its also after one century that arrives the first treatment derived from biotechnological research that aims allergies which is the most commonly known expression of an anaphylactic reaction.

In 1913 Charles Richet received the Nobel Prize of Medicine and Physiology for his work on anaphylaxis, which he discovered with Paul Portier in 1902. The 335 letters received by Charles Richet shortly thereafter shed some light on his position in the European world at the time. In the field of biomedical sciences, he distinguished himself with his constant determination to blend physiology, and clinical studies, which irritated the fundamentalists and clinicians at the time; The circumspection of the latter in regard to anaphylaxis is evident in their letters. For wasn't anaphylaxis an experimental pathogen occurence, devoid obvious clinical correlations, in comparison to Pasteur's immunology with its serums and vaccinations, firmly relevant to modern medicine? An abundant non-biological correspondence arrived from various horizons-cultural, literary, metapsychistnatalist, pacifist, as well as those concerned with civil justice and civil liberties, the Intellectuals. Strangely, Charles Richet, who was actively engaged in such struggles, is barely mentioned in the index of recent works devoted to the role played by these Intellectuals. Was Charles not an Intellectual? Or has the expression come to mean something different today?

At the birth of the scientific thoughts, the degree of creativity of the searcher depends on his capacity to extract himself from the previously acquired notions in this domain. The discovery of anaphylaxis, by Charles Richet and Paul Portier, constitutes therefore an epistemological break off, knocking over the theory on organism defences and the universality of the biological response to different stimuli. In the light of the works of Charles Richet on hypnosis, renal physiology, thermoregulation and psychophysiology, we see that the most creative discoveries are also the most unexpected or the most difficult to impose. They require courage and initiative, severity of thought, a radical independence of mind and a certain distance concerning eventual practical consequences.

The paper provides a historical overview of the discovery of both histamine and the H1 antihistamines. The context of these discoveries is provided in relation to the development of medicinal chemistry during the 19th century. Background is provided on the history of discovery of mechanisms of anaphylaxis and allergy and the immunology of hypersensitivity at the end of the 19th and early 20th century. The discovery of histamine and the antihistamines is then discussed in relation to the development of pharmacological receptor theory culminating in the discovery of the first antihistamines in the 1930s and their widespread clinical introduction in the 1940s.

While studying the toxicology of various coelenteres fishing filament poisons, Charles Richet and Paul Portier observed cases of rapid death which had no correlation with the injected doses. In dogs, death only occurred in those which, more than 15 days beforehand, had withstood well an injection more concentrated or identical to the later fatal one. The authors created the neologism 'anaphylaxis' which signifies 'non-protection'. Thus, it appeared that an immune response could be pathological. This discovery opened the subject area of immunopathology at a period of time when, in contrast, vaccination and serotherapy researches were prominent.

Two years after graduating from medical school, Ivan Mota decided to spend a year doing postgraduate training. Little did he realise that he was embarking on a course that would see him lay the foundations for modern research into allergy and anaphylaxis. Here, he recounts his own tale.

Anaphylaxis appears to be an excellent experimental model for investigating the interactions between central nervous system (CNS) and immune system. Both afferent and efferent regulatory pathways of anaphylactic response are well characterized. The potent mediators of anaphylactic shock, such as histamine and serotonin, are at the same time neurotransmitters, acting in the CNS, and regulators/modulators of the immune system, since receptors for these substances exist on the membrane of the cells of the immune system. In this article the results of studies on the relationship between anaphylaxis and CNS, performed by both pioneers and contemporary investigators, are briefly reviewed. Recent experiments done in our laboratory are presented, which showed that (a) anaphylactic shock can be induced by intracerebroventricular administration of the shocking dose of antigen; (b) rats can learn to associate the induction of anaphylactic shock with neutral stimuli from the environment; and (c) stress in the form of electric tail-shocks reduces the intensity of anaphylactic shock.