Canine endotoxic shock causes profound mesenteric vasoconstriction and eventual necrosis of the bowel wall. These findings are thought to result from endogenous catecholamine release and have given rise to a theory that the gut is a target organ which mediates the progression of hypotension into irreversible shock. To assess this theory the effects of endotoxin on the mesenteric circulation were studied in anesthetized baboons. Mesenteric blood flow was measured with an electromagnetic flowmeter. Mesenteric vascular resistance was calculated from the measured arterial-portal pressure gradient divided by flow. Following intravenous endotoxin (Escherichia coli) there was a progressive and significant fall in arterial pressure within 2 hr. Blood flow and portal pressure remained unaltered by endotoxin during the 4 hr following its injection. As a result resistance fell progressively and at 2 hr the value was significantly below control. Thus mesenteric hemodynamic events following endotoxemia in the primate differ considerably from those in the dog, a finding first observed in the rhesus monkey. This study confirms this earlier observation in a primate phylogenetically closer to man. The data suggest that the target organ theory is not applicable to shock therapy in man.