Phenotypic expressions of apolipoprotein E (apo E) were studied in 94 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 91 normal controls. The apo E gene frequencies observed in patients with NIDDM (epsilon 4, 0.101; epsilon 3, 0.824; and epsilon 2, 0.075) were not significantly different from those in normal controls (epsilon 4, 0.093; epsilon 3, 0.863; and epsilon 2, 0.044). Subgrouping the diabetic patients with and without hyperlipidemia, the epsilon 2 allele was significantly more frequent in patients with hypertriglyceridemia. The levels of serum triglyceride, very low density lipoprotein-cholesterol (VLDL-C), and VLDL-triglyceride (VLDL-TG) were significantly higher in patients with the epsilon 2 heterozygote than in those without the epsilon 2 allele (P less than .01). The results suggest that variation in the apo E gene may be one factor related to the hypertriglyceridemia present in patients with NIDDM.