Familial clustering of coronary artery disease (CAD) and familial influences on various clinical and metabolic risk factors were investigated in 85 male survivors of acute myocardial infarction younger than 45 years. The study also involved 85 age-matched men randomly selected from the general population and the first-degree relatives of both patients and control subjects. Presence of CAD was assessed by an angina questionnaire and from rest and exercise electrocardiograms. There was an apparent aggregation of premature CAD in 38% of the case families. A familial clustering of hyperlipoproteinemia was present in 58% of the case families and 15% of the control families. Systemic hypertension and cigarette smoking also were clustered in the case families. Multivariate statistical analyses of clinical and metabolic risk indicators in patients with and without a family history of CAD and in control subjects indicated that familial aggregation of CAD is independently related to MI at a young age. Degree and extent of coronary atheromatosis and number and severity of hemodynamically significant stenoses did not differ between young patients with and without a familial aggregation of CAD. The absence of a relation between the family history and severity of CAD implies that other underlying mechanisms are involved.