Abstract The role of apolipoproteinE (apoE) phenotypes in modulating the plasma lipid and lipoprotein levels was studied in a group of NIDDM patients and healthy individuals residing in Mumbai. The apoE phenotype frequencies were similar in the diabetic and healthy persons. The elevations in the lipid/lipoprotein levels were higher in diabetic subjects (53.3%) than in the controls (8%), showing the frequency of increase to be highest in the apoE4/4 group of diabetics, followed by apoE4/3 and apoE3/2 groups. In the controls as well, a similar trend was observed in different groups, indicating that the susceptibility to changes in lipid concentrations differs among apoE phenotypes. The apoE3/3 bearing individuals in both the categories showed close to normal lipid levels, suggesting it to be the wild type. The occurrence of apoE4 allele was higher than the apoE2 allele in diabetic individuals. Diabetic subjects with the apoE4 allele showed hypercholesterolemia, while those with apoE2 showed the presence of hypertriglyceridemia. One of the striking features of our work is a significant relationship between apoE4/3 phenotype in NIDDM persons and elevated levels of plasma triglyceride, thus suggesting a delayed catabolism of VLDL relative to production. In conclusion, the work suggests that the apoE2 and apoE4 alleles are associated with elevations in lipid levels and these changes are more pronounced in the diabetic individuals in whom most of the lipid levels were higher, indicating a gene–environment/disease interaction.