Estrogen replacement therapy is widely used to treat menopausal symptoms and prevent osteoporosis. The mechanism of these and other estrogen effects is currently under investigation. We studied the plasma steroid hormone and sex hormone binding globulin levels in frozen plasma obtained from 977 women aged 50 to 79 years from 1972 to 1974. Almost all of the 301 women who reported current use of noncontraceptive estrogen were taking conjugated estrogen by mouth; none reported use of a progestin. Women taking estrogen were significantly younger, thinner, and more likely to smoke cigarettes than women not taking estrogen. Sex hormone binding globulin and all endogenous hormones except testosterone were negatively correlated with age; estradiol was positively and cortisol and sex hormone binding globulin were negatively associated with obesity. After adjusting for age and obesity, dehydroepiandrosterone sulfate, androstenedione, and free testosterone were significantly lower in women currently taking estrogen than in women not using estrogen. These differences were independent of cigarette smoking. As expected, estrogens (including free estradiol), sex hormone binding globulin, and cortisol levels were higher in treated than untreated women. The possibility that some of the benefits and risks of replacement estrogen are secondary to altered adrenal steroid metabolism and androgen levels needs further evaluation.