A genetic-epidemiologic study was undertaken of a white Colorado population of 207 patients who had a myocardial infarction before age 55 years. Nineteen independent variables were compared between the 207 cases and 621 controls, matched 3:1. The highest risk ratios were associated with a positive family history for ischemic heart disease (IHD). The heritability of IHD was 63% when families with the monogenic forms of hyperlipoproteinemia were included, and 56% when they were excluded. A risk index was developed that incorporates family history into a data base of risk factors, which can be readily assessed by the clinician obtaining a screening history, physical and standard laboratory tests. A scale of 0-10 was devised and the predictive value of the index was tested against another data set. The efficiency of the index was maximal at a screening level of 5. This study suggests that it is logistically feasible to seek patients at high risk for intensive management in a clinical setting (high-risk strategy) using risk indices similar to the one developed for this study, which emphasize the very important familial component to IHD.