The impact of the three most common apolipoprotein E (APOE) genotypes (epsilon 32, epsilson 33, and epsilon 43) on means, variances, and correlations of nine plasma lipid and apolipoprotein traits (total cholesterol, InTriglycerides, HDL cholesterol, and apolipoproteins AI, AII, B, CII, CIII, and InE) was studied in 212 unrelated female and 219 unrelated male children aged 5-21.5 years from 278 pedigrees ascertained without regard to health status from Rochester, Minnesota. There was significant heterogeneity (p < or = 0.05) among genotypes for the mean plasma levels of InApo E, Apo CII, Apo CIII, and InTriglycerides (InTrig) in females, and for the means of InApo E, Apo B, and total cholesterol (Total-C) in males. Significant heterogeneity of intragenotypic variance was observed in males for Apo CII, InTrig, and HDL-C; no significant heterogeneity was observed in females. Pairwise correlations between traits differed significantly among APOE genotypes in both females (6 of 36 pairs) and males (5 of 36 pairs). These results differ from those obtained from studies of the parental generation from the same sample of pedigrees. Our study further demonstrates that, with the exception of mean InApo E levels, the univariate and bivariate distributions of traits that are measures of lipoprotein metabolism are influenced by variation in the APOE gene in a gender- and generation-dependent manner.