The prevalence of an uncommon allelic variant (S2) of the apoprotein AI-CIII-AIV gene cluster was determined in non-insulin-dependent diabetics with or without evidence of coronary heart disease and in controls. Frequencies of the S2 allele were 14% for diabetics with coronary heart disease compared with 2% for non-diabetics with no clinical evidence of occlusive vascular disease. No subject with the S2 allele was detected among a further group of matched diabetics without clinical features of macrovascular disease. The results suggest that a genetic component contributes to the susceptibility to coronary heart disease in non-insulin-dependent diabetics. Whether the observed deoxyribonucleic acid variant is aetiological for atherosclerosis or in linkage disequilibrium with other atherogenic loci on chromosome 11 remains to be clarified.