A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.