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Leukocyte exchange between the hemopoietic tissues of parabiotic rats was studied subsequent to giving multiple injections of 3H-thymidine to one member of each pair while arresting the cross-circulation. Cell types that migrated from one parabiont to the other were segmented granulocytes, small, medium and large lymphocytes, immunoblasts, monocytoid cells, macrophages or their immediate precursors, and plasma cells. Evidence for the transformation of circulating cells to other cell types was rarely seen. The long-lived small lymphocytes were equilibrated between parabionts, suggesting that this is a single pool of cells with respect to kinetic behavior and recirculation. There was no evidence for a trephocytic function of lymphocytes. A small number of bone marrow lymphocytes coursed directly to lymph nodes and spleen. Evidence is given for a limited recirculation of short-lived lymphocytes of thoracic duct lymph (TDL), as well as for long-lived cells. Only a few immunoblasts of TDL recirculated. The majority of cells that entered the white pulp of the spleen were long-lived small lymphocytes, while the majority of immigrant cells to the red pulp were monocytoid cells and granulocytes. Many small lymphocytes originated in splenic red pulp and entered the blood. No immigrant cells to the thymic cortex were noted, although some small lymphocytes and monocytoid cells entered the medullary areas. Immigrant cells to the bone marrow (less than 2% of the cells in marrow) included monocytoid cells, small lymphocytes, and plasma cells. Evidence for the direct transformation of a circulating cell into a committed blast, based on reduction in grain count, was noted only in bone marrow.

These radioautographic studies using parabiotic rats and partial marrow shielding showed that cells responsible for recovery of irradiated bone marrow had their origin in the shielded marrow. Three morphologically distinct cell types appeared in the blood of these parabionts, mature granulocytes, small lymphocytes and monocytoid cells. The monocytoid was the major cell type which crossed from the shielded to nonshielded marrow, and the observations suggested that it is this cell which served as a stem cell for both the erythrocytic and granulocytic cell lines. Labeled erythroblasts and myeloblasts were observed in the recovering marrow, and the labeling intensity of these cells indicated that they were the second or third division products of labeled immigrant cells. The effect of marrow shielding upon the recovery of lymphopoiesis in spleen, thymus, lymph nodes and bone marrow is also discussed.

Single and multiple injections of tritiated thymidine were combined with radioautography to study the rates of proliferation and interrelationships of the various cell lines in the mesenteric lymph node of the rat. The appearance and labeling patterns of the different cells are described from studies of both smears and tissue sections. Reticular cells exhibit wide variations in labeling intensity, phagocytize labeled lymphocytes, and become labeled in high percentages only when TTH is administered over a period of many days. Other slowly proliferating cell types include small lymphocytes, fat cells, endothelial cells and mast cells. Rapidly proliferating cell lines include plasmablasts, hemohistioblasts, proplasmacytes and large lymphocytes. The generation time of plasmablasts and hemohistioblasts was determined to be approximately 9 and 12 hours respectively. Mature plasma cells constitute a non-dividing population which is renewed in lymph node in not more than 5 days. Evidence is presented that the most primitive cells in the lymphocyte and plasma cell lines are the hemohistioblasts and plasmablasts respectively. Reticular cells most probably are not stem cells. No evidence is found to support previous reports that plasma cells derive from lymphocytes.

Radioautography with tritiated thymidine has been utilized to examine the turnover rate and origin of small lymphocytes in the bone marrow of the guinea-pig. Very few marrow lymphocytes were initially labeled by a single injection of tritiated thymidine, but thereafter the number of labeled lymphocytes rapidly increased to high maximum levels at 3 days. Analysis of the labeling curves and grain counts indicates that the population of marrow lymphocytes is maintained in a dynamic steady state with an average turnover time of 3 days or less. Suspensions of bone marrow cells were isolated from the circulation within intraperitoneal diffusion chambers after short-term labeling with tritiated thymidine in vivo. Although very few small lymphocytes were labeled when introduced into the diffusion chambers, a considerable percentage became labeled during the subsequent culture period. Tritiated thymidine was also administered intravenously whilst excluded from one hind limb by the application of an occlusive compression bandage for 20 minutes. Very few labeled small lymphocytes were found after 72 hours in the tibial marrow of the initially occluded limb, whereas the normal high percentage was labeled in the control tibial marrow. These experiments do not demonstrate any large-scale influx of small lymphocytes from the blood stream into the marrow parenchyma. They suggest that newly formed small lymphocytes appear in the marrow as a result of the division of locally situated precursor cells, but the mechanism of intramedullary lymphocytopoiesis is uncertain. "Transitional" cells, intermediate in morphology between blast cells and small lymphocytes, synthesize DNA and are actively proliferative, but they do not appear to account fully for the rate of lymphocyte production. Certain large, undifferentiated labeled cells appeared in the bone marrow as a result of hematogenous migration. Some implications of these findings are discussed.

Tritium-labeled thymidine was given by either intraperitoneal or intravenous injection to 13 male guinea pigs of approximately 400 Gm. weight. At times varying from 1 hour to 30 days after the administration of thymidine, thoracic duct lymph was obtained and examined for the presence of labeled cells. After a single dose of thymidine, a steady stream of labeled lymphocytes, ranging from 2 to 7 per cent of the total cells, enters the blood over the period studied. The intensity of the labeling appears to diminish gradually. Labeled large and medium lymphocytes were found in the lymph during the first hour. Labeled small lymphocytes began to appear in the fourth hour, in small numbers, and thereafter increased, whereas the proportion of labeled large and medium lymphocytes steadily diminished. This sequential appearance of large, medium and small lymphocytes is interpreted as indicating the pattern of development of the cell series. The labeled small lymphocytes appearing in the lymph are considered to be newly formed from precursor cells located in the various lymphatic tissues.

(i) Morphological studies relating to the origin and differentiation of the definitive germ cells in vertebrates have, as indicated, resulted in conflicting views. In many instances two or more competent investigators who have studied the same form have reached different conclusions. (2) Some contend that the germ cells are set aside from the soma during the early stages of embryonic development, and that these alone serve as the progenitors of the functional sex cells. (3) Others recognize an early differentiation of sex cells but hold that these are supplemented by others produced from the somatic epithelium of the gonad in late embryonic or post‐embryonic stages. (4) Another group recognizes the early differentiated cells as germ cells but contend that these all degenerate and that the definitive ones are formed from the germinal epithelium. These degenerating germ cells are believed by certain authors to be a phylogenetic recapitulation of the condition in lower forms. (5) Finally, yet another group contends that the so‐called primordial germ cells are not germ cells at all but are enlarged cells in some stage of mitosis or in some specific metabolic phase. This group believes that all germ cells are derived from the somatic cells of the germinal epithelium. (6) Experimental work supports the view that the primordial germ cells, which are recognized early, are the progenitors of the definitive sex cells. When these primordial germ cells are prevented from reaching the site of the developing gonad the individual fails to develop sex cells, although a sterile gonad and its associated structures may develop. (7) I suggest that the observed proliferation of germ cells from the germinal epithelium, reported by numerous investigators, can be interpreted in another way by a thorough study of the enlarged germ cells in relation to the epithelium. It seems probable that the cells of the epithelium, which form functional sex elements, are not and never were a part of the mesothelial covering, but are cells which were segregated early, and are merely stored in the epithelium.