The centrally mediated cardiovascular effects of Escherichia coli endotoxin were studied utilizing a neurally intact vascularly isolated head-trunk preparation in the anesthetized dog. The vascularly isolated head was perfused at constant flow with arterial blood supplied by a donor animal. Spectrophotometric examination of the donor and recipient trunk blood after administration of Evan's blue dye indicated that there was no blood exchanged between the head and trunk of the recipient dog. The responses to various physiological maneuvers and denervations indicated that the central nervous system and all afferents and efferents involved in the control of the cardiovascular system were functioning normally. The infusion of purified E. coli endotoxin into the arterial perfusion circuit to the head, either before or after bilateral denervation of the carotid sinus-body complexes, resulted in marked hypotension within 30 minutes in the trunk of the recipient dog. These findings indicate that purified E. coli endotoxin is capable of eliciting marked centrally mediated hypotensive responses. The time course of these responses suggests that the centrally mediated hypotensive effects of endotoxin do not participate in the initial precipitous fall in blood pressure seen after systemic administration of endotoxin, but rather that they may contribute significantly to the maintenance of the hypotension.