A national sample of 1944 white menopausal women greater than or equal to 55 years old from the epidemiologic follow-up of participants in the National Health and Nutrition Examination Survey was reviewed to investigate the role of hormone therapy in altering the risk of death from cardiovascular disease. Women in the study were observed for up to 16 years after the baseline survey in 1971 to 1975. By 1987 631 women had died; 347 of these deaths were due to cardiovascular disease. History of diabetes (relative risk, 2.38; 95% confidence interval 1.73 to 3.26), previous myocardial infarction (relative risk, 2.12; 95% confidence interval 1.56 to 2.86), smoking (relative risk, 2.18; 95% confidence interval, 1.69 to 2.81), and elevated blood pressure (relative risk, 1.49; 95% confidence interval, 1.14 to 1.94) were strong predictors of cardiovascular disease-related death in this cohort. After adjusting for known cardiovascular disease risk factors (smoking, cholesterol, body mass index, blood pressure, previous myocardial infarction, history of diabetes, age) and education, the use of postmenopausal hormones was associated with a reduced risk of death from cardiovascular disease (relative risk, 0.66; 95% confidence interval, 0.48 to 0.90). The same protective effect provided by postmenopausal hormone therapy was seen in women who experienced natural menopause (relative risk, 0.69; 95% confidence interval, 0.45 to 1.06).