Apolipoprotein E (ApoE), and especially its epsilon4 isoform, is considered a risk factor predisposing to coronary heart disease. We hypothesized that the absence of epsilon4 allele offers a better chance for longer life. So we compared the prevalence of ApoE genotypes in 80 healthy aged individuals (HAI) (>80 years) and 391 Greek adults (median age 43 years) with ApoE genotype distribution consistent with the Hardy-Weinberg equilibrium (chi(2) = 5.93, p >.05). ApoE genotypes were comparable in both groups with the exception of E3/3 and E3/4, which were significantly higher (87.50% vs 75.99%, p =.025) and lower (5.00% vs 13.19%, p =.036), respectively, in HAI. The epsilon2 and epsilon3 allele frequencies were not different between the groups. The epsilon4 allele was significantly less frequent in HAI compared to controls (3.1% vs 8.58%, p =.020). Our results indicate an unfavorable effect of epsilon4 allele on longevity that may be attenuated by environmental and/or other genetic factors.