The protective effects of high dose antenatal vitamin E on hypoxemia in newborn rats were investigated. The subjects were 1-d-old Wistar rats weighing 5-6 g which were born to mothers weighing 245-250 g. Three groups of rat pups, each consisting of eight newborn rats, were used: nontreated control group, hypoxic group, and vitamin E group. The mothers of pups in the last group were given vitamin E (2000 mg/kg/d) antenatally on 3 consecutive days. Hypoxia was induced by breathing of a mixture of 8% oxygen and 92% nitrogen for 3 h. Then pups were allowed to inhale normal atmospheric air for 30 min. All rats were killed on the first day of life after the procedure of hypoxia and reoxygenation. The brains, lungs, livers, intestines, and kidneys were studied biochemically and histopathologically. The hypoxia-induced biochemical changes were determined by measuring lipid peroxidation and myeloperoxidase activity. Vitamin E effectively inhibited hypoxia-induced lipid peroxidation in liver and intestines, and decreased the levels of thiobarbituric acid-reactive substances in brain. In agreement with lipid peroxidation, tissue associated myeloperoxidase activity was increased in liver, intestines, and kidneys, but not in brain and lungs, of the hypoxic group. Histopathologic changes in intestines were epithelial separation and submucosal polymorphonuclear leukocyte infiltration. In the liver, leukocyte infiltration was observed only near the portal areas. These changes were not observed in the vitamin E group. It was concluded that high doses of antenatal vitamin E may protect the newborn rat pups against hypoxia-induced tissue injury.