Interferon alpha has been used widely to treat hepatitis B virus infection in children. However, the overall initial response rates have been < 50% and several strategies have been attempted to improve this. The aim of this study was to evaluate the safety and efficacy of prolonged interferon alpha treatment in children who did not respond to a previous course of interferon alpha treatment. Twenty-seven children with chronic hepatitis B who had not responded to a 6-month course of interferon alpha 2a (5 MU/m2 body surface) thrice weekly subcutaneously continued to receive interferon alpha at the same dosage for another 6 months without a rest phase. The children were followed for 6 months after completing 12 months of therapy. All of them had HBsAg, HBV-DNA and HBeAg tested on completion of the first course. Six of the 27 (22.2%) cleared both HBV-DNA and HBeAg after completion of therapy and all six had a sustained response. Pre-treatment predictive factors were not significantly associated with treatment response. No adverse effect of interferon was seen during follow-up. We conclude that prolonged interferon treatment is well tolerated and leads to additional benefit.