Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C-reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians. This cross-sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40-year-olds, and 70-year-olds). In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of epsilon2/2, epsilon2/3, epsilon3/3, epsilon2/4, epsilon3/4 and epsilon4/4. Total (P= 0.009) and low-density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the epsilon4 allele carriers. In newborns, the epsilon4 frequency was 0.192, in 40-year-olds 0.181, in 70-year-olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the epsilon4 allele frequency in the elderly was more clearly seen in women than in men. APOEepsilon4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some epsilon4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.