Objective: To investigate whether a redistribution of blood flow from the mucosa to the muscular layer of the intestinal wall con tributes to the observed increased arterial-mucosal Pco(2) gradient and the decreased mucosal tonometric pH during endotoxic shock. Design: A prospective, controlled, animal study. Setting: Animal laboratory in a university medical center, Subjects: Ten domestic pigs. Interventions: Pigs were anesthetized with ketamine and pentobarbital, mechanically ventilated, hemodynamically monitored, and then challenged with Escherichia coil endotoxin (10 mu g/kg iv). Measurements and Main Results: Cardiac output, mesenteric artery blood flow, and systemic, pulmonary, and portal pressures were measured, Intestinal mucosa tonometric Pco(2) and pH were determined with saline-filled balloon tonometers, The tissue blood flow to the mucosa and the muscular layer were independently measured with colored microspheres, using the arterial reference sample method, Thus, total intestinal blood flow was evaluated with respect to its transmural (mucosa vs, muscularis) and geographical (proximal jejunum, mid-small intestine, and terminal ileum) distribution. Endotoxin administration with fluid resuscitation induced a distributive shock with a decrease in intestinal mucosa tonometric pH. Under endotoxemic conditions, the mucosal flow increased in each geographical area, with the increase being larger proximally in the jejunum than distally in the ileum, The mucosal tonometric pH was found to correlate inversely with mucosal blood flow, The increase in blood flow to the mucosa was balanced by a decrease in blood flow to the muscularis, with total mesenteric flow remaining unchanged. Conclusions: Mucosal hypoperfusion does not account for the acidotic mucosal tonometric pH in endotoxic shock. The results suggest either a primary cytotoxic effect or an enhanced countercurrent-mediated hypoxic insult in the apical villus. The decrease in blood flow to the muscularis may contribute to loss of intestinal wall peristaltic activity and structural wall integrity.