We examined apolipoprotein E (apo E) allele frequencies in non-insulin-dependent diabetes mellitus (NIDDM) patients with normolipidemia or various types of hypertriglyceridemia to elucidate the association of the apo E alleles with hypertriglyceridemia in NIDDM. NIDDM patients with normolipidemia (N = 134) or hypertriglyceridemia [type IIb hyperlipoproteinemia (HLP) (N = 42), III HLP (N = 7), IV HLP (N = 96), and V HLP (N = 8)] were randomly selected from our Diabetic Clinics. Apo E phenotypes (genotypes) were determined by our rapid flat-gel isoelectric focusing method. The frequency of the ε4 allele was significantly higher in the type IIb (20.2%, P < .01) and V (25.0%, P < .05) HLP patients than in the normolipidemic patients (8.9%), whereas the frequency of the ε3 allele was significantly ( P < .025) lower in the type IIb HLP patients (78.6%) than in the normolipidemic patients (89.2%). The frequency of the ε2 allele was significantly higher in the type III (64.3%, P < .001) and IV (5.2%, P < .05) HLP patients than in the normolipidemic patients (1.9%), whereas the frequency of the ε3 allele was significantly lower in the type III (28.6%, P < .001) and IV (82.8%, P < .05) HLP patients than in the normolipidemic patients. Thus, it has proven that the ε2 allele is related to type III and IV HLP in NIDDM, whereas the ε4 allele is related to type IIb and V HLP in NIDDM. It is concluded that the ε4 allele, as well as the ε2 allele, may, at least in part, contribute to hypertriglyceridemia and probably atherosclerosis in NIDDM.