This study addressed the possible influence of apolipoprotein E (apo E) genotype on age-related changes in total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and triglyceride (TG) levels in older males. Apo E is a component of LDL, is a ligand for the LDL receptor, and apo E genotype has been consistently associated with variation in mean levels of TC and LDL-C, and also appears to influence TG levels. Using male twins followed longitudinally between mean ages of 48 and 63 years, the change in TC, LDL-C, and TG over time for individuals with the epsilon 3 epsilon 3 and the epsilon 3 epsilon 4 genotypes was contrasted. At exam 1 mean TC and LDL-C levels were lower in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group, but at exam 3 mean TC and LDL-C levels were significantly higher in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group. The rate of change in TC and LDL-C with age differed significantly between epsilon 3 epsilon 3 and epsilon 3 epsilon 4 groups. Results for TG were not statistically significantly. These findings suggest that the apo E genotype effects on risk of coronary artery disease may be age-dependent. This study demonstrates the value of longitudinal studies in refining models for genetic risk factors for disease.