Apolipoprotein E (apo E) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease. The extent to which serial patterns of change in total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations varied by apo E genotype was therefore investigated in 247 Caucasian girls aged 8 to 14 at baseline who were participating in Project HeartBeat!, a mixed longitudinal study of cardiovascular disease (CVD) risk factor development in children. Plasma lipid concentrations were determined for each participant three times per year (every 4 months) for up to 4 years from October 1991 through August 1995. Mean total cholesterol values for individuals with epsilon2/3, epsilon3/3, and epsilon3/4 genotypes were 141.7, 161.6, and 165.9 mg/dL, respectively (P < .001). Corresponding LDL-C values for individuals with epsilon2/3, epsilon3/3, and epsilon3/4 genotypes were 74.6, 94.8, and 98.7 mg/dL, respectively (P < .001). The results of longitudinal modeling indicated that age trajectories for total cholesterol and LDL-C varied significantly by apo E genotype. Individuals with epsilon3/3 and epsilon3/4 genotypes exhibited similar patterns of change in total cholesterol and LDL-C from ages 8 to 18, while individuals with the epsilon2/3 genotype demonstrated a significantly different pattern of change (age2 x genotype interaction, P < .05). For example, individuals with the epsilon2/3 genotype showed a slight increase in total cholesterol from approximately 141 to 146 mg/dL from ages 8 to 10; total cholesterol then decreased monotonically from ages 10 to 18 from 146 to 115 mg/dL. The apo E effect on total cholesterol and LDL-C and their change during adolescence is strong and may be modified by factors affecting growth, maturation, and reproductive function.