To elucidate the effect of smoking on estrogen metabolism, we examined 136 postmenopausal women treated for one year with one of three different doses of combined estrogen-progestogen or placebo. The women were grouped according to smoking status, and serum levels of estrone and estradiol were measured before and after treatment. The results showed reduced levels of both estrogens in smokers as compared with nonsmokers in all three dosage groups. This reduction was most pronounced in the high-dose group (4 mg of estradiol), in which the serum levels of estrone and estradiol in smokers were only 50 per cent of those in nonsmokers (P less than 0.001 and less than 0.05, respectively). In contrast, no significant changes could be demonstrated in the corresponding placebo groups. Moreover, it was possible to demonstrate significant inverse correlations between the number of cigarettes smoked daily and the changes in the levels of serum estrone and estradiol, respectively, (P less than 0.001). This study suggests that an increased hepatic metabolism of estrogens results in lower estrogen levels among postmenopausal smokers. This may contribute to the reported risk of osteoporosis among smokers.