A significant difference was observed between developmental patterns of metyrapone reductase activities in liver microsomes of male and female rats. The activity in liver microsomes of male rats was maintained at high levels until ten weeks of age after birth. In contrast, the activity in liver microsomes of female rats was markedly decreased until six weeks of age and reached low levels after eight weeks of age. As with the results of such different patterns, there were pronounced sex-related differences during adult period. Castration significantly decreased the activity in liver microsomes of male rats. This finding suggests that androgens have a role in sex-related differences of the activities in liver,microsomes of male and female rats. Furthermore, sex-related differences of the activities were examined in microsomes and cytosol from the liver and kidney of the rat, mouse, hamster, guinea pig, and rabbit. All animal species tested showed sex-related differences in their activities. The rat and rabbit were found to resemble the guinea pig and hamster, respectively, in the occurrence of sex-related difference.