The relationship between apolipoprotein (apo) E phenotypes and the levels of plasma lipid, lipoprotein and apo E in young (mean, 21 years of age) and middle-aged (mean, 49 years of age) subjects was investigated. Apo E phenotypes were determined by a rapid flat gel isoelectric focusing method that we had developed previously. Young subjects with apo E3/2 and E4/3 had significantly higher levels of plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG and VLDL-cholesterol than those with apo E3/3. Middle-aged subjects with apo E3/2 (54.5%) and E4/3 (39.1%) had higher frequency of hyperlipoproteinemia (mainly type IV) than those with apo E3/3 (25.8%). Furthermore, the middle-aged subjects with apo E3/2 had significantly higher levels of plasma TG, VLDL-TG and apo E, and significantly lower levels of plasma high density lipoprotein-cholesterol than those with apo E3/3. These results indicate that apo E phenotype E3/2 and E4/3 are associated with lipid abnormalities even in young subjects, which may be caused by impaired functions of apo E2 and E4.