The cytokine pattern secreted by T cells on viral antigen recognition is believed to exert a profound influence on both the type of disease caused by the infecting agent and the final outcome of the viral infection. To characterize the cytokine pattern associated with spontaneous resolution of acute hepatitis B, we analyzed interferen gamma (IFN-γ), interleukin (IL)- 4, and IL-5 production by a wide series of hepatitis B virus (HBV) nucleocapsid-specific T-cell lines (34 lines) and T-cell clones (71 clones) derived from the peripheral blood of 13 patients during the acute or recovery phase of hepatitis B (2 and 7 of them were studied only in the recovery or the acute phase, respectively, and 4 during both). Most T-cell lines (67%) and clones (77%) isolated during the acute phase of infection expressed a T- helper (Th) 1 cytokine profile dominated by the production of IFN-γ. A larger proportion (74%) of T-cell lines produced several years after resolution of hepatitis was able to secrete not only IFN-γ, but also IL-4 and IL-5 (Th0-like cells). Results indicate that the antigen-specific fraction of peripheral blood T cells in acute self-limited hepatitis B selectively secrete Th1-type cytokines, suggesting that Th1-mediated effects may contribute not only to liver cell injury, but probably also to recovery from disease and successful control of infection.