The peripheral vascular response to Escherichia coli endotoxin (1 mg/kg/i.v.) was measured for 2 hr in the pentobarbital anesthetized dog. Total venous return was collected and returned by a pump to the right atrium to maintain a constant cardiac output. Occlusion of the venous lines permitted estimation of venous compliance in the systems drained by the superior (SVC) and inferior vena cavae (IVC). After endotoxin administration, arterial pressure and total peripheral resistance rapidly dropped and remained low for 2 hr. IVC compliance was decreased at 10-30 min and SVC compliance at 10 min after endotoxin. The decrease in compliance is interpreted as venous dilation and probably venous pooling. The latter may account for a substantial portion of the total venous pooling reported in early endotoxin shock. After 30 min, compliance increased and by 60 min was equal to control. Left ventricular relaxation ability decreased as indicated by maximal negative dp/dt. Ibuprofen, 10 mg/kg, was administered at 120 min or earlier, depending on the state of the animal; rapid recovery of arterial pressure and ventricular function occurred without a significant change in venous compliance.