The risk of family history of ischemic heart disease independent of other well described risk factors has remained difficult to quantitate. Significant coronary artery disease was determined by coronary arteriography to be present in 223 patients and absent in 57 control subjects. Age, sex, blood pressure, serum cholesterol, cigarette smoking and the presence of diabetes and left ventricular hypertrophy on the electrocardiogram were tabulated for each patient and the data used to assign a risk score based on the American Heart Association multivariate model. Subjects were stratified and matched according to risk score to estimate risk of family history independent of familial aggregation of these seven other risk factors. Angina, myocardial infarction, cardiac death and any ischemic heart disease were ascertained in 1,319 first degree relatives. Odds ratios for overall, stratified and matched comparisons of these end points in relatives of patients and control subjects ranged between 2.0 and 3.9 (p less than 0.01 for all comparisons), indicating a higher frequency of all ischemic heart disease end points in relatives of patients with documented coronary artery disease. Life table comparison of patients at lowest risk with those at higher risk showed significantly greater cumulative frequency and earlier age of onset of all ischemic heart disease end points in relatives of low risk patients. These observations indicate that some of the risk associated with family history is independent of familial aggregation of other known risk factors and suggest that the independent effects of family history may be most important in individuals who otherwise are at low risk.