The lipoprotein(a) [Lp(a)] and apolipoprotein E (apoE) polymorphisms have been shown to be important genetic determinants of cardiovascular risk. Their effect on coronary heart disease (CHD) is less clear, particularly in Asian Indians who are at high risk for this disease. The aim of this study was to examine the association of the Lp(a) promoter pentanucleotide repeat polymorphism and the apoE codon 112 and 158 genotypes in 195 young South African Indian patients (< or = 45 years) with myocardial infarction (MI). Results were compared with 300 healthy age-matched control subjects drawn from the same community and 107 unaffected siblings (18-45 years). In addition, fasting lipograms were performed on all patients and a detailed history of conventional risk factors and family background was obtained. Of the six different Lp(a) alleles detected, the 8-repeat sequence was most frequently seen. However, no difference in frequencies existed between patient and control groups. The most frequently occurring apoE genotype in the three study groups was E3/E3 (patients 71%; siblings 70%; controls 70%). A significant difference in the E3/E4 genotype was seen between patients and controls (23% vs 14%; p = 0.018) and between siblings and controls (24% vs 14%; p = 0.027). These patients were also more likely to have significantly higher low-density lipoprotein (LDL) and lower high-density lipoprotein (HDL) levels (p = 0.005 and 0.045, respectively). No association was observed between any of the Lp(a) or apoE genotypes and conventional risk factors such as smoking, diabetes, hypertension, obesity or a family history of CHD. In conclusion, the apoE3/E4 genotype is strongly associated with the incidence of myocardial infarction in young South African Indians. This genotype also adversely affects LDL and HDL cholesterol levels, both of which contribute to premature atherosclerosis. In contrast, the Lp(a) pentanucleotide repeat polymorphism does not appear to have any aetiological role in MI in this population.