In mature male rats both estradiol administration as well as castration had a striking suppressive effect on the hepatic activity of the microsomal ethanol-oxidizing system, whereas alcohol dehydrogenase activity was increased under these experimental conditions. The castration effects on the activities of the alcohol-metabolizing enzymes could be completely prevented by the administration of testosterone. Therefore, these results indicate the sex-dependent nature of the hepatic microsomal ethanol-oxidizing system and alcohol dehydrogenase.