The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30–65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X2=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X2=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.