Free radical mechanisms have been implicated in mediating tissue damage after ischemia in several different organ systems. Vitamin E serves as a major defense against free radical injury and vitamin E deficiency may be a contributing factor in the increased vulnerability of newborn and preterm infants to ischemic injury. Therefore we set up an ischemic gut model in the rat to study the effects of vitamin E deficiency and repletion on free radical propagation and on mucosal enzyme levels. Weanling Sprague-Dawley rats were placed on vitamin E deficient or replete diets for 13-15 wks and then subjected to a 45 min cranial mesenteric artery occlusion and 15 min reperfusion or timed laparotomy. Mucosal scrapings from jejunum and ileura were homogenized and assayed for in vitro lipid peroxidation ustng thiobarbituric acid assay of malondialdehyde. In addition, a mucosal enzyme, sucrase, was measured in jejunal homogenates. Increased lipid peroxidation was seen in vitamin E deficient small bowel and this was further increased after ischemia. Vitamin E added to the assay in vitro or given to the rats in vivo prevented this increased lipid peroxidation. A higher concentration of vitamin E was needed for inhibition of lipid peroxidation after ischemic insult. Ischemia resulted in a decrease in sucrase in jejunum of vitamin E deficient but not in vitamin E replete rats. Thus vitamin E deficiency potentiates the effect of ischemia on free radical formation, and enhances the acute functional gut damage, as measured by a decrement in mucosal enzyme activity.