Activated T helper (Th) cell-dependent (TD) antibody responses were determined over an 8-10 year period in 28 patients infected with HIV-1 subtype B. Twelve patients remain asymptomatic with normal CD4+ cell counts for 101-114 months. These individuals were defined as long-term asymptomatic (LTA). Sixteen patients progressed to severe immunodeficiency within 58-120 months. In samples derived close to the diagnosis of HIV-1, CD4+ cell counts were higher among the LTAs (P < 0.01). Antibody production driven by activated Th cells was determined using peptides corresponding to HIV-1 V3US/Eur, gp41, and the hepatitis C virus (HCV) core proteins. The less Th cell-dependent B cell antibody response was represented by measles virus immunity. Close to HIV-1 diagnosis, variable third (V3), gp41, HCV core, and measles antibody titres were at similar levels among the LTAs and the progressors. With time the LTAs displayed unchanged levels of V3 and gp41 antibodies, and slightly decreasing levels of HCV core antibodies (P < 0.05). In contrast, the progressors showed a decrease in all these antibody responses (P < 0.05, for all). In both groups, the levels of measles antibody remained stable. Our data show that no significant change of the antibody responses of LTAs is seen, even after 101-114 months of known HIV-1 infection. Furthermore, the marked decrease of TD antibody production in the progressors suggests that activated Th cells may be excellent targets for HIV-1 infection.