['Prooxidant effects of fish oil supplementation could unfavorably affect the cardiovascular benefits of fish oil. We tested the effects of 8 wk vitamin E cosupplementation with fish oil on antioxidant defenses at rest and in response to exhaustive exercise in rats.', 'Rats (N = 80) were divided into fish oil, fish oil and vitamin E (FOVE), soy oil, and soy oil and vitamin E (SOVE) supplemented groups. For the vitamin E supplemented rats, corresponding groups (FOVE-Ex and SOVE-Ex) performed an acute bout of exhaustive exercise after the supplementation period.', 'Fish oil supplementation increased the activity of catalase, glutathione peroxidase, and glutathione-S-transferase in the liver and red gastrocnemius (RG) muscle. Fish oil decreased liver total glutathione (TGSH) levels. Vitamin E supplementation decreased antioxidant enzyme activities to levels at or near those in SOVE in a tissue specific pattern. Vitamin E increased TGSH in liver, heart, and RG. Regression analysis showed TGSH to be a negative determinant of protein oxidative damage as measured by protein carbonyl levels in both liver and RG. Catalase activity was associated with liver lipid peroxidation as measured by thiobarbituric acid-reacting substances. The exercise-induced decrease in hepatic TGSH tended to be less in FOVE versus SOVE. Exhaustive exercise also modulated tissue antioxidant enzymes.'] Does vitamin E regulate changes in tissue antioxidants induced by fish oil and acute exercise?