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Rats were fed with diets containing differing amounts of α-tocopherol for 21 days. For the latter 14 days of this period, one half of the rats also received ethanol (7% v/v) in the drinking water. Treatments did not alter the rate of weight gain between groups. Hepatic glutathione levels were depressed by ethanol treatment in rats receiving diets deficient in α-tocopherol or containing normal levels of the vitamin (50 ppm). However, this depression was not found in rats maintained on a high α-tocopherol diet (1000 ppm). The high α-tocopherol diet also prevented the ethanol-induced inhibition of proteolytic activity within the liver. A dose-dependent reduction of rates of hepatic generation of reactive oxygen species was effected by this vitamin. Within the central nervous system, the only region showing an ethanol-induced lowering of glutathione levels, was the midbrain of rats receiving the α-tocopherol deficient diet.