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 epsilon 4 allele was significantly higher in the type IIb (20.2%, P less than .01) and V (25.0%, P less than .05) HLP patients than in the normolipidemic patients (8.9%), whereas the frequency of the epsilon 3 allele was significantly (P less than .025) lower in the type IIb HLP patients (78.6%) than in the normolipidemic patients (89.2%). The frequency of the epsilon 2 allele was significantly higher in the type III (64.3%, P less than .001) and IV (5.2%, P less than .05) HLP patients than in the normolipidemic patients (1.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type III (28.6%, P less than .001) and IV (82.8%, P less than .05) HLP patients than in the normolipidemic patients. Thus, it has proven that the epsilon 2 allele is related to type III and IV HLP in NIDDM, whereas the epsilon 4 allele is related to type IIb and V HLP in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)