The primary immune response to a viral antigen (tick-borne encephalitis, TBE) has been determined in haemophiliacs. Twelve HIV-negative and four clinically asymptomatic, HIV-positive haemophiliacs as well as 16 age-matched healthy controls were included in the study. Antibody responses after TBE vaccination were comparable in HIV-negative haemophiliacs and controls; however, antibody titres in HIV-infected haemophiliacs were significantly lower after completion of the three-dose vaccination schedule (geometric mean reciprocal antibody titres (SEM): controls, 193 (1.37), HIV-positive haemophiliacs, 13 (2.18), P < 0.005). TBE vaccination failed to induce a T cell proliferative response in the HIV-positive haemophiliacs. While in HIV-negative patients the antigen-specific lymphoproliferative responses after primary and one booster vaccination were comparable to those of the controls, cellular responses were decreased in HIV-negative haemophiliacs following a second booster immunization 19 months after primary immunization (3H-thymidine incorporation, delta dpm, mean +/- SEM: controls, 34662 +/- 7129, HIV-negative haemophiliacs, 14339 +/- 7420, P < 0.005). As the protective mechanisms for TBE infection are not yet completely understood, further work will be necessary to determine whether the decreased capacity to mount a sufficient long-term cellular memory response in HIV-negative haemophiliacs might be important for the protective effect of TBE vaccination in this population.