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Simple Summary: Both wild (Sorghum halepense) and cultivated Sorghum (Sorghum bicolor) species are commonly used for animal feeding. However, sorghum plants naturally produce dhurrin, a cyanogenic glycoside releasing cyanide; this extremely toxic molecule potentially causes lethal toxicoses, particularly in ruminants. This was the case in a number of farms located in Northwest Italy during August 2022, under weather conditions (drought, tropical temperatures) known to increase plants' dhurrin content. Sixty-six bovines died after grazing Sorghum pastures (Sorghum bicolor or Sorghum halepense) or being fed with Sorghum-containing hay (Sorghum halepense). The reported clinico-pathological findings clearly indicated cyanide poisoning, and chemical analysis revealed high concentrations of dhurrin in the plant materials. The successful management of such toxicosis should rely on the prompt removal of the contaminated fodder and the administration of the antidote sodium thiosulphate. Dhurrin content should be carefully monitored, particularly in the hot season, and both farmers and veterinarians should be made aware of the risks associated with feeding cattle even with cultivated Sorghum, particularly if grown under adverse climatic conditions. Sorghum plants naturally produce dhurrin, a cyanogenic glycoside that may be hydrolysed to cyanide, resulting in often-lethal toxicoses. Ruminants are particularly sensitive to cyanogenic glycosides due to the active role of rumen microbiota in dhurrin hydrolysis. This work provides an overview of a poisoning outbreak that occurred in 5 farms in Northwest Italy in August 2022; a total of 66 cows died, and many others developed acute toxicosis after being fed on either cultivated (Sorghum bicolor) or wild Sorghum (Sorghum halepense). Clinical signs were recorded, and all cows received antidotal/supportive therapy. Dead animals were subjected to necropsy, and dhurrin content was determined in Sorghum specimens using an LC–MS/MS method. Rapid onset, severe respiratory distress, recumbency and convulsions were the main clinical features; bright red blood, a bitter almond smell and lung emphysema were consistently observed on necropsy. The combined i.v. and oral administration of sodium thiosulphate resulted in a rapid improvement of clinical signs. Dhurrin concentrations corresponding to cyanide levels higher than the tolerated threshold of 200 mg/kg were detected in sorghum specimens from 4 out of 5 involved farms; thereafter, such levels declined, reaching tolerable concentrations in September–October. Feeding cattle with wild or cultivated Sorghum as green fodder is a common practice in Northern Italy, especially in summer. However, care should be taken in case of adverse climatic conditions, such as severe drought and tropical temperatures (characterising summer 2022), which are reported to increase dhurrin synthesis and storage. [ABSTRACT FROM AUTHOR]