Hepatitis B virus (HBV) is mainly transmitted during birth or perinatal period, however, treatment is not usually recommended for pediatric patients with chronic hepatitis B (CHB). Twelve pediatric patients with CHB in Bangladesh were treated with both lamivudine and interferon. Lamivudine was given at a dose of 3 mg/kg, daily for 12 months. Two months after commencement of lamivudine therapy, all patents were given interferon-alpha (3 million IU/square meter of body surface area) three times weekly, subcutaneously for 10 months. Combination therapy was safe for all pediatric CHB patients. The levels of serum HBV DNA became undetectable (less than 500 copies/ml) in 8 patients and reduced in 4 patients after the end of therapy. Anti-HBe was detected in 10 of 12 patients at this time point. The levels of serum alanine aminotransferase (ALT) were significantly reduced in these patients (p less than 0.05) due to therapy. Neither flare of HBV DNA nor elevation of serum ALT were detected during follow-up. In conclusion, combination therapy with lamivudine and interferon-alpha represents a new and novel therapeutic option for treatment of pediatric CHB patients.