Plasma obtained and frozen in 1972-1974 from 1,009 white men (40-79 years old) who have been followed for 12 years was examined for endogenous sex hormone levels according to prevalent or subsequent cardiovascular disease. In these older men, no sex hormone measured (testosterone, androstenedione, estrone, or estradiol) was significantly associated with known cardiovascular disease at baseline or with subsequent cardiovascular mortality or ischemic heart disease morbidity or mortality. Sex hormone-binding globulin levels were also similar by disease status. Analyses of hormone: sex hormone-binding globulin ratios or of estrogen: androgen ratios showed a similar lack of association with cardiovascular disease. Testosterone levels were significantly inversely associated with levels of blood pressure, fasting plasma glucose, and triglyceride and body mass index. In contrast, the only significant estrogen risk factor associations were positive correlations of estrone with total plasma cholesterol, triglyceride, and glucose. These data do not support a causal role for elevated endogenous estrogen levels and heart disease. (Circulation 1988;78:539-545) Among the many risk factors for cardiovascular disease, few are more important than male sex.1'2 Several case-control studies have tested the hypothesis that one or more endogenous sex hormones are related to cardiovascular disease risk in men. Most investigators found significantly elevated endogenous estrone and/or estradiol levels,3-10 but some reported significantly lower testosterone levels3 11-13 or no significant difference in estrogens or testosterone14,15 in men who had survived a myocardial infarction compared with men who had not had an infarction. Based on results of coronary angiography, some case-control studies reported higher levels of estradiol in men who had coronary artery stenosis compared with men without coronary artery stenosis,16,17 but a majority did not.6,10,18-20 One prospective study of endogenous sex hormones and cardiovascular risk has been published, the 6-8-year follow-up of