The response of the small intestinal vascular bed to endotoxin and ibuprofen was determined in mongrel dogs under pentobarbital anesthesia. Blood flow was measured in the superior mesenteric artery and pressures in the artery and portal vein. Venous compliance was calculated from the rate of pressure rise in the occluded portal vein at a constant arterial inflow. The response to endotoxin was followed for 1 hr, ibuprofen was given, and the response was followed for a second hour. Arterial pressure and mesenteric flow decreased after endotoxin, accompanied by an increase in venous compliance and in the compliance/resistance ratio. Treatment with ibuprofen increased arterial pressure but did not improve blood flow; however, it effectively reversed the changes in compliance. The results indicate a loss of arterial vasomotor tone in response to endotoxin which is not shared by the portal venous system. This may result in fluid loss into the intestinal bed. Ibuprofen restored arterial tone and released the venous constriction, but did not significantly alter the metabolic responses to endotoxin.