In order to determine the frequencies of apolipoproteins (ape) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common ape E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with:h faster migration and E5s slower migration. The gene frequencies were: the epsilon 3 allele, 0.841; the epsilon 4 allele, 0.095; the epsilon 2 allele, 0.049; the epsilon 7 allele, 0.009; the epsilon 5 allele encoding apo E5f (the epsilon 5f allele), 0.004; and the epsilon 5 allele encoding ape E5s (the epsilon 5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and ape E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that ape E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.