The characterization of immune responses to hepatitis B virus is crucial for the understanding of hepatitis B virus–caused liver disease. However, lack of a suitable autologous effector–target cell system makes a precise study of the pathogenesis of hepatitis B difficult. In this study we established a model system by using autologous HBcAg-expressing Epstein-Barr virus–immortalized lymphoblastoid cell lines as stimulator/target cells. T-cell cultures were established by repetitive stimulation with recombinant HBcAg or autologous HBcAg-expressing lymphoblastoid cell lines. Both proliferative and cytotoxic T-cell clones were obtained from the peripheral blood of an asymptomatic HBsAg carrier. Clones T12 (CD8+) and T2B (CD4+) were cytotoxic clones specific against autologous lymphoblastoid cell lines expressing endogenously synthesized HBcAg, whereas five CD4+ T-cell clones proliferated in response to lymphoblastoid cell lines incubated with exogenous recombinant HBcAg and autologous HBcAg-expressing lymphoblastoid cell lines. These results indicate that autologous HBcAg-expressing lymphoblastoid cell lines are appropriate stimulator/target cells for the study of HBcAg-specific T lymphocytes. By using this approach, we have demonstrated that both proliferative and cytotoxic T lymphocytes recognizing endogenously synthesized HBcAg are induced during chronic hepatitis B virus infection. (HEPATOLOGY 1993;18:275–283).