Hepatitis B virus(HBV)-specific cytotoxic T lymphocytes(CTLs) are believed to play a major role in viral clearance and disease pathogenesis during HBV infection.To clarify the differences in host immune responses between self-limited and chronic HBV infections,we constructed three HLA-A*0201/HBV tetramers with immunodominant epitopes of core18-27,polymerase 575-583 and envelope 335-343,and analyzed the HBV-specific CTLs in peripheral blood mononu-clear cells(PBMCs) from patients infected with HBV.The frequencies and expansion ability of HBV-specific CD8+ T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients.HBV-specific CD8+ T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA.In chronic infection,no significant correlation was found either between the frequencies of HBV-specific CD8+ T cells and the viral load,or between the frequencies and the levels of alanine transaminase.Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immuno-therapeutic approaches should be aimed at not only boosting a HBV-specific CD8+ T response but also improving its function.