To determine the relation of menopause to the risk of coronary heart disease, we analyzed data on a prospective cohort of 121,700 U.S. women 30 to 55 years old who were followed from 1976 to 1982. Information on menopausal status, the type of menopause, and other risk factors was obtained in 1976 and updated every two years by mailing questionnaires. Through 1982, the follow-up rate was 98.3 percent for mortality and 95.4 percent for nonfatal events. After we controlled for age and cigarette smoking, women who had had a natural menopause and who had never taken replacement estrogen had no appreciable increase in the risk of coronary heart disease, as compared with premenopausal women (adjusted rate ratio, 1.2; 95 percent confidence limits, 0.8 and 1.8). Again compared with premenopausal women, the occurrence of a natural menopause together with the use of estrogens did not affect the risk (rate ratio, 0.8, 95 percent confidence limits, 0.4 and 1.3). Women who had undergone bilateral oophorectomy and who had never taken estrogens after menopause had an increased risk (rate ratio, 2.2; 95 percent confidence limits, 1.2 and 4.2). However, the use of estrogens in the postmenopausal period appeared to eliminate this increased risk among these women as compared with premenopausal women (rate ratio, 0.9; 95 percent confidence limits, 0.6 and 1.6). These data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease. This increase appears to be prevented by estrogen-replacement therapy.