SUMMARY: Liver microsomes derived from male rats were shown to convert a higher proportion of [14C]oestrone and [14C]oestradiol to water-soluble products than did similar preparations from female rats. This sex difference became apparent at maturity and could be influenced by castration or treatment with sex hormones. The increased formation of water-soluble material by male rats was accompanied by an increase in the yield of 2-hydroxyoestradiol and other ether-soluble metabolites but no sex difference in oestrogen metabolism was detected in mice or guinea-pigs and the effect was less pronounced with [14C]stilboestrol as substrate. The enzyme system influenced by the hormonal status of the animals was present in the microsomes and showed similarities to the non-specific oxygenases which hydroxylate steroids and a number of drugs.