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.