The authors investigated the association of serum copper concentration with the risk of acute myocardial infarction in 1,666 randomly selected men aged 42, 48, 54, or 60 years who had no symptomatic ischemic heart disease at entry. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study in Eastern Finland were done during 1984 to 1988. In Cox multivariate survival models adjusting for age, examination year, ischemic electrocardiogram in exercise, maximal oxygen uptake, diabetes, family history of ischemic heart disease, cigarette-years, mean systolic blood pressure, serum high density lipoprotein (HDL) cholesterol subfraction HDL2 and low density lipoprotein (LDL) cholesterol concentrations and blood leukocyte count, serum copper concentration in the two highest tertiles (1.02-1.16 mg/liter and 1.17 mg/liter or more) associated with 3.5-fold (95% confidence interval (Cl) 1.3-9.4, p less than 0.05) and 4.0-fold (95 percent Cl 1.5-10.8, p less than 0.01) risk of acute myocardial infarction. These data indicate that high copper status, reflected by elevated serum copper concentration, is an independent risk factor for ischemic heart disease.