Selenium is a trace mineral that plays a role in antioxidant defenses as a component of glutathione peroxidase. Epidemiologic findings on the relation of selenium status to risk of heart disease are inconsistent. Therefore, the authors investigated prospectively the association between toenail selenium levels and risk of coronary heart disease (CHD) in a case-control study nested within the Health Professionals Follow-up Study. Between 1987 and 1992, 470 CHD cases were newly diagnosed. A control matched to each case on age, smoking status, and date of toenail return was chosen. Toenail selenium levels analyzed by neutron activation were not associated with risk of total CHD after adjustment for age and smoking and other CHD risk factors (highest quintile vs. lowest: odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.55, 1.32; p-trend = 0.75). Selenium level was inversely associated with risk of nonfatal myocardial infarction for extreme quintiles (OR = 0.54, 95% CI: 0.31, 0.93; p-trend = 0.07), was less so for fatal CHD (OR = 0.79, 95% CI: 0.39, 1.60; p-trend = 0.61), and was directly associated with coronary revascularization procedures (OR = 2.38, 95% CI: 1.11, 5.09; p-trend = 0.02). Although these findings suggest no overall relation between selenium status and CHD, a specific protective role for myocardial infarction cannot be excluded.