This follow-up report from the Nurses' Health Study evaluated women age 30-55 for the effects of hormone replacement therapy on the occurrence of myocardial infarction or death from coronary disease and cerebral vascular accidents. From 1976 to 1992, 770 cases of myocardial infarction or death and 572 strokes were identified. A marked decrese in the risk of major coronary heart disease among women who took estrogen and progesterone, as compared with risk among women who did not use hormones, was identified (multivariate adjusted relative risk, 0.39; 95% confidence interval, 0.19, 0.78). The estrogen-alone population relative risk was 0.60 (95% confidence interval, 0.43, 0.83). No significant association between stroke and the use of combined hormones or estrogen alone was identified. There was a trend toward an increased risk of stroke with higher doses (0.625 mg) of estrogen. Hormone-related protection against coronary artery disease appears to diminish somewhat 3 years following cessation of therapy. The relative risk of coronary artery disease in women who had ceased to use hormone replacement therapy for <3 years was 0.69, whereas 3-4.9 years after cessation, the relative risk was 0.81. The authors concluded that the addition of progestin does not appear to attenuate the cardioprotective effects of postmenopausal estrogen therapy.