An antiestrogenic effect of cigarette smoking has been suggested, principally on the basis of data on premenopausal women. We examined the relation between cigarette smoking and endogenous sex-hormone levels in a population of 233 white, postmenopausal women 60 to 79 years of age. Current cigarette smokers had significantly higher mean plasma levels of the adrenal androgens dehydroepiandrosterone sulfate and androstenedione than nonsmokers. Mean levels for smokers and nonsmokers were 3.1 mumol per liter (116 micrograms per deciliter) and 2.3 mumol per liter (86 micrograms per deciliter), respectively (P less than 0.001), for dehydroepiandrosterone sulfate, and 27.8 nmol per liter (797 pg per milliliter) and 22.5 nmol per liter (643 pg per milliliter), respectively (P = 0.002), for androstenedione. A dose-response relation was apparent for these hormones; mean plasma levels increased concomitantly with cigarette consumption. The differences in hormone levels remained after adjustment for age and body-mass index. Mean levels of estrone, estradiol, testosterone, and sex-hormone-binding globulin did not differ between smokers and nonsmokers. These results suggest that the possible decreased risk of breast and endometrial cancer associated with cigarette smoking may not be mediated through lower levels of endogenous estrogen, at least in postmenopausal women, and they raise questions about the role of androgens in disease mechanisms in older populations.