The aim of our study is to determine the role of oxidative stress on hepatic damage in patients with acute and chronic hepatitis B virus (HBV) infection and the efficacy of antioxidant-enzyme system against oxidative stress. Furthermore, the effect of interferon-alpha (IFN-alpha) plus lamivudine therapy on oxidative stress was also investigated. Nineteen patients with acute hepatitis B virus (AHBV) infection, 17 patients with chronic hepatitis B virus (CHBV) infection, 24 inactive HBsAg carriers and 21 healthy controls were included in the study. In control and patient groups, serum alanine-aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte malondialdehyde (MDA) levels, erythrocyte superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities were measured. In CHBV group, after IFN-alpha plus lamivudine therapy for 6 months, these parameters were measured again. In all patient groups erythrocyte MDA levels were detected higher than control group (p<0.05). Activity of CuZn-SOD was found to be the highest in AHBV (p<0.05), and the lowest before the treatment in CHBV group (p<0.05) compared with other groups. Activity of GSH-Px was found to be the highest in AHBV compared with inactive HBsAg carriers (p<0.05) and CHBV group before treatment (p<0.05). Activity of GSH-Px was found to be the lowest in CHBV group before treatment compared with other groups (p<0.05). In CHBV group there was a significant decrease of MDA levels after treatment (p<0.05) while there was a significant increase in activity of CuZn-SOD and GSH-Px compared with pretreatment levels (p<0.05). A significant positive correlation was determined between MDA values and serum ALT levels, before and after the treatment (p<0.05). Detection of the increase of MDA levels which is a product of lipid peroxidation in all patient groups, indicates that the oxidative stress is increased in HBV infection. Correlation between the levels of erythrocyte MDA levels and serum ALT levels supports the hypothesis concerning the role of oxidative stress in pathogenesis of HBV infection. Insufficiency of antioxidant capacity in CHBV and inactive HBsAg carrier groups may lead to progression of disease and results in fibrosis. Treatment with IFN-alpha plus lamivudine causes a decrease in products of lipid peroxidation and shows antioxidant activity via increasing the antioxidant enzymes. These data suggest that the addition of antioxidant agents to IFN-alpha and lamivudin combination therapy may be useful in CHBV treatment. Further in-vitro and in-vivo studies are required to enlighten the role of antioxidants on HBV disease progression and treatment.