BACKGROUND: Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efifcacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment. METHODS: Twenty patients with CHB proven by liver biopsy, with ALT levels>1.5×ULN, HBV DNA levels>141 500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5 μg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was deifned as normalization of ALT and DNA response as HBV DNA