Although treatment with high dose exogenous sex hormones affects cardiovascular risk, the role of physiological levels of endogenous sex hormones in the development of atherosclerotic disease in men and women is unknown. Forty men and 43 women wit peripheral arterial disease and 88 age- and sex-matched controls were selected from participants in the Edinburgh Artery Study, a random survey of 1592 men and women ages 55-74 years from the general population. Compared with sex-matched controls, male cases had higher systolic blood pressure (155.5 mmHg vs. 138.7 mmHg; p < or = 0.01) and waist hip ratio (0.92 vs. 0.89; p < or = 0.05) and female cases had higher lifetime smoking (square root of packyears 2.14 vs. 1.03; p < or = 0.05). Mean estrone levels were slightly higher in male cases than controls (101.9 pmol/Liter vs. 92.1 pmol/Liter; p = 0.09), but this association lost significance after multivariate adjustment for age and body mass index. Mean levels of total and free testosterone, estradiol, and sex hormone binding globulin were not significantly different in cases compared with controls in either sex (p > 0.1). These results, in accordance with previous prospective studies on coronary artery disease, do not support a role for physiological levels of endogenous sex hormones in the development of peripheral arterial disease in men or postmenopausal women.