Department of Physiology and Biophysics, West Virginia University School of Medicine, Morgantown, West Virginia 26506, U.S.A. (Received 25 June 1976) Many studies have established the importance of the gonadal hormones in the regulation of hepatic steroid and drug metabolism in rats (Yates, Herbst & Urquhart, 1958; Kitay, 1963; Conney, 1967; Gillette, Davies & Sasame, 1972). The activity of hepatic steroid Δ4-hydrogenase, the rate-limiting step in corticosteroid metabolism, is enhanced by oestradiol and diminished by testosterone administration. Consequently livers from female rats metabolize corticosteroids more rapidly than those from male rats. In contrast the metabolism of many drug substrates by hepatic microsomal cytochrome P-450-containing enzymes is increased by testosterone (Quinn, Axelrod & Brodie, 1958) and inhibited by oestradiol (Murphy & DuBois, 1958), resulting in a sex difference in oxidative drug metabolism opposite to that in reductive (Δ4-hydrogenase) steroid metabolism. We recently reported that the effects of gonadal hormone on both hepatic