The intestinal mucosal lesion caused by low-flow states may lead to grave consequences. In a series of canine experiments, the superior mesenteric arteries were clamped for 60 minutes. Significant protection of the intestinal mucosa was obtained with glucose introduced into the lumen of the bowel as soon as possible after the onset of ischemia. Morphological damage was minimized, and the mucosal adenosine triphosphate content increased. Mannitol is not normally absorbed from the intestine. Intraluminal mannitol, with a concentration equivalent osmotically to that of glucose, failed to protect intestinal mucosa from ischemia. Furthermore, the tissue lactate in the mucosa of sacs containing glucose was elevated. It appears, therefore, that glucose acted by virtue of its role as an energy substrate rather than by an osmotic effect.