Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are thought to play key roles in viral control and liver damage. We have used HLA-A*02 tetramer complex to human HBV core 18-27 (Tc 18-27), envelope 183-191 (Te 183-191), envelope 335-343 (Te 335-343), and polymerase 575-583 (Tp 575-583) epitopes to characterize HLA class I-restricted CD8+ T cells in active chronic HBV infection. The frequencies of specific epitopes circulating tetramer+ cells were determined in whole-blood samples by analysis of flow cytometry. The correlation of HBV epitope-specific CTL, between viral replication and liver damage, was analyzed by multiple regression. Our data shown that HBV-specific CD8+ T cells can be easily detected in peripheral blood of active chronic HBV infections. No significant correlation was found between either the frequency of HBV-specific CD8+ T cells and the viral load, or the frequency of HBV-specific CD8+ T cells and the levels of alanine transaminase. These results suggest that the existence of epitope-specific HBV CTLs are not directly correlated to hepatocyte injury, and the frequencies of HBV-specific T cells are not determinant of immune-mediated protection in chronic HBV infection.