The influence of apolipoprotein (apo) E polymorphism on serum lipoproteins from childhood to adulthood was examined in 1520 individuals, aged 5-14 years at baseline, followed over a 16-year period. At both times, the e2 allele associated with lower LDL cholesterol (P < 0.001) and higher HDL cholesterol (P < 0.05-0.01), the e4 allele with higher LDL cholesterol (P < 0.001). The e2 allele lowered the adulthood LDL cholesterol level to a greater extent than the childhood level (P < 0.05). With respect to tracking, at the lowest quartile of LDL cholesterol distribution, the persistence in ranks over time was higher in the apoE2 group with E2/3 and E2/2 phenotypes compared with the apoE3 group with E3/3 phenotype and the apoE4 group with E3/4 and E4/4 phenotypes (P = 0.001). Longitudinal increases in the ponderal index (weight/height3) lowered the adulthood HDL cholesterol to a larger extent in e2 carriers (P = 0.017). The interindividual variability in LDL cholesterol due to childhood and adulthood ponderal index was 1.8- to 2.3-fold greater in the apoE2 group versus the apoE3 group. Likewise, cigarette smoking, alcohol use and oral contraceptive use in adulthood explained greater variability in triglycerides (5.3-fold), VLDL cholesterol (7.8-fold) and HDL cholesterol (2.9-fold) in the apoE2 group versus the apoE3 group. Thus, the apoE locus influences not only the levels and tracking of certain lipoproteins from childhood to adulthood but also modulates the association between lifestyle-related factors and lipoproteins.