A significantly lower frequency of the epsilon 2 allele and a significantly higher frequency of the epsilon 3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (epsilon 2, epsilon 3 and epsilon 4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, VLDL-cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)-C and high density lipoprotein (HDL)-C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the epsilon 2 allele had an effect to increase the TG, VLDL-TG, VLDL-C and apo E levels and decrease the TC, LDL-C and HDL-C levels, whereas the epsilon 4 allele had an effect opposite to the epsilon 2 allele. These results indicate that the epsilon 2 and epsilon 4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels.