The aim of this study was to verify whether or not the increased prevalence of coronary heart disease (CHD) commonly observed in patients with type 2 diabetes mellitus is related to a genetic background involving restriction fragment length polymorphisms (RFLPs) of apolipoproteins. On the basis of a case-control design, 62 type 2 diabetic patients with CHD (confirmed by clinical history and electrocardiogram) and 62 age- and sex-matched diabetic subjects without CHD were enrolled. In each of them RFLPs of the apolipoproteins levels, were assessed. The rare S2 allel was found significantly (P=0.05) more frequently in patients with CHD, and its related S1S2 genotype was associated with higher plasma levels of total cholesterol (P=0.01), triglycerides (P=0.007) and apo B (P=0.001) than the S1S1 genotype. The A allele was more frequent (P=0.004) in patients without CHD and was associated with lower plasma cholesterol (P=0.0001), and low-density lipoprotein (LDL)-cholesterol (P=0.0001) and apo B (P=0.005). The S1/A haplotype was more frequent (P=0.05) in patients without CHD and was associated with the lowest plasma lipid levels. These results suggest that genetic factors, related to the apo AI-CIII-AIV gene cluster, could play a role in the development of CHD in type 2 diabetic patients, probably through modification of their plasma lipid pattern.