Greater than one-half of children with chronic hepatitis B infection are nonresponders to interferon-alpha (IFN-alpha). The aim of this study was to investigate the efficacy of lamivudine (LMV) and IFN-alpha combination therapy in these children. Nineteen children were given LMV alone for 3 months; then IFN-alpha was added to LMV for 6 months. Virologic response was achieved in seven (36.8%) patients. LMV and IFN-alpha combination therapy may represent an effective treatment option.