At the light of the importance of cytotoxic T lymphocyte (CTL) response during chronic hepatitis C, we carried out a study in order to evaluate the CD8+/CD38+T-cells, immunophenotypic marker of CD8+ activated cells in a selected cohort of 22 patients for four months. The patients were subdivided in two groups: A (with IFN therapy), B (without IFN therapy). The results show that in IFN-treated subjects there is a significant reduction of ALT (sign test, z = .424;p < or = .05) and that the CD8+/CD38+ present a positive correlation with HCV-RNA (r = .894; p < .05). We hypothesize that during IFN therapy the CD8+/CD38+ activity is able to oppose HCV, probably by increasing MHC I expression on the infected cells due to the IFN modulatory action, that could strengthen the immune response of CD8+ activated T-lymphocytes. These events confer the capacity to specifically respond to any viral replication and probably take part in the reduction of ALT levels by decreasing the chronic inflammation present during a defective immune response. These data show think CD8+/CD38+ marker could be a good parameter to evaluate both the viral activity and immunological status in HCV+ patients undergoing IFN treatment.