Endotoxin in eight unanesthetized monkeys produced a small decrease in cardiac output, a marked fall in blood pressure, and a decrease in total peripheral vascular resistance. The distribution of cardiac output was measured by injecting nuclide-labeled radioactive microspheres (50µ in diameter) into the left ventricle, and blood flow and vascular resistance were calculated for each organ. All vascular beds except that of the spleen reacted with variable degrees of vasodilation, and the most pronounced decreases in resistance were observed in the coronary, gastrointestinal, and adrenal vasculature. Cerebral flow was reduced, but flow was maintained in the brain stem and cerebellum. In contrast to studies in other species, both the gastrointestinal tract and the kidneys showed vasodilation and no significant decrease in flow during the early phase of endotoxemia. There is some similar evidence in humans of decreased total systemic peripheral resistance without abnormal myocardial function or pooling of blood during the early phase of endotoxemia. The acute regional circulatory changes we have found appear to indicate that endotoxin either directly or through secondary biochemical reactions initiates and maintains a generalized (except for the spleen) vasodilation that reflex compensatory mechanisms cannot overcome. This vasodilation is particularly critical in preventing maintenance of adequate blood flow to the cerebral hemispheres.