The patho-genesis of irreversible arterial hypotension in the primate administered endotoxin is not understood. Studies were carried out on 13 Sooty Mangabey monkeys under conditions of total body perfusion. Experiments were designed to determine the relative roles of venous return, cardiac output, and total peripheral resistance in the development of irreversible systemic hypotension after endotoxin. Hemo-dynamic parameters of control preparations not given endotoxin were observed to be stable over a 60-min perfusion period. Results indicate that the primary cause of progressively developing systemic arterial hypotension is a continuous decline in venous return. Decreases in total peripheral resistance were observed in all monkeys given endotoxin but were also seen in two controls. Hemo-concentration was absent in both experimental and control monkeys. Changes in certain metabolic parameters suggest derangement of tissue metabolism in shocked animals. Cause of the failure of total peripheral resistance to increase in the face of sustained arterial hypotension is unknown. Sites of pooling are postulated to be widely generalized in postcapillary vascular segments.