To study whether individual Human Leucocyte Antigens (HLA) at the HLA 1 or 11 loci or the phenotypic combination A1B8Cw7DR3 were associated with longevity. Direct comparison of the > 90-year-old subjects with a control group. Northern Ireland population with little migratory mobility. The > 90-year-old group (79 females, 38 males) was compared with a control group consisting of 150 unrelated blood donors (81 females, 69 males). Human Leucocyte Antigen (HLA) Class 1 typing was carried out on 117 nonagenarians (mean age 93.7 years) and 150 younger controls (mean age 33.7 years) using conventional serological methods; HLA DR typing was carried out on 102 of the 117 > 90-year-old subjects, together with the 150 control subjects, and performed using restriction fragment length polymorphisms. The frequency of the phenotypic combination A1B8Cw7DR3 was measured in both groups. There were no significant differences in the HLA antigen frequencies between the very elderly groups and the younger subjects at the A, B, C, and DR loci. The phenotypic combination A1B8Cw7DR3 was significantly increased (X3) in nonagenarian men compared with young men but not between elderly women and young women. There was a trend for increased representation of this phenotype in elderly men compared with women of the same age. The frequency of the supratype A1B8Cw7DR3 was significantly increased in very elderly men but not in elderly women. Since this phenotypic combination has been associated with immune surveillance and/or hyperactivity in Caucasians, there is the suggestion that it could influence longevity through immune mechanisms but that sex differences may exist in its influence and expression.