We conducted a prospective controlled study of the efficacy of recombinant interferon-alpha 2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-alpha 2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received megaunits/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p < 0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-alpha 2a accelerates HBeAg-HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-alpha 2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse.