We compared the frequencies of HLA antigens in two matched groups of 31 HIV-seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981-85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs.