Since an elevated serum concentration of lipoprotein(a) [Lp(a)] associated with a positive family history of premature myocardial infarction (PMI), would support the hypothesis that Lp(a) is a genetic risk factor for atherosclerosis, we measured serum levels in subjects from families with a history of PMI and compared them to those in a group of healthy control subjects. Twenty-five males (average age 39 +/- 16 years) and 9 females (average age 42 +/- 14 years) who had at least one blood relative affected by PMI were included in the study; 20 males (average age 41 +/- 11 years) and 10 females (average age 37 +/- 13 years) served as control subjects. Serum cholesterol, triglyceride, HDL-cholesterol, apo A1, apo B100 and Lp(a) concentrations were measured in both groups. The statistically significant higher prevalence of elevated Lp(a) levels (> 30 mg/dL) in the PMI group (p < 0.05) is attributable to the higher prevalence of PMI males with elevated Lp(a) levels. Pedigree studies disclosed a family distribution of coronary heart disease compatible with the hypothesis of a segregation of a dominant character for PMI risk. Because serum Lp(a) concentration is inherited with a Mendelian codominant pattern, we conclude that our data strongly support the hypothesis of a correlation between excess Lp(a) and coronary atherosclerosis.