The ability of triglyceride (TG)-rich lipoproteins from apolipoprotein (apo) E2 heterozygote, apo E3/2 which is relatively common, to stimulate cholesteryl ester synthesis in human monocyte-derived macrophages was studied to clarify the atherogenicity of apo E3/2. Twenty-three subjects were randomly sampled from our hospitals, and divided into the following 4 groups: 7 apo E3/3 subjects with normolipidemia, 6 apo E3/3 subjects with hypertriglyceridemia (HTG), 5 apo E3/2 subjects with normolipidemia and 5 apo E3/2 subjects with HTG. Plasma levels of TG and total cholesterol (chol) were significantly (P < 0.001) higher in apo E3/3 and apo E3/2 subjects with HTG than in apo E3/3 and apo E3/2 subjects with normolipidemia, but plasma levels of TG and total chol were not significantly different between apo E3/3 and apo E3/2 subjects with HTG. [14C]oleate incorporation into cholesteryl esters in macrophages was significantly (P < 0.001) higher in apo E3/2 subjects with HTG (0.661 nmol/mg cell protein) than in apo E3/3 subjects with normolipidemia (0.228) and with HTG (0.325) and in apo E3/2 subjects with normolipidemia (0.257). It is concluded that TG-rich lipoproteins from apolipoprotein E3/2 subjects with HTG enhance cholesteryl ester synthesis in human macrophages.