A total of 24 chronic carriers of HBsAg, HBeAg and hepatitis B virus (HBV)-DNA were included in a controlled trial. The patients were randomly assigned to four groups: Group I (n = 6): control; group II (n = 6): 2.5 MU; group III (n = 6): 5 MU and group IV (n = 6): 10 MU rIFN-alpha/m2 body surface 3 times weekly i.m. during 6 months. At the end of the treatment, all patients under therapy, as well as 4 belonging to the control group, lost HBV-DNA polymerase. HBV-DNA became negative in 3 (50%), 1 (17%), and 2 (33%) patients from groups II, III, and IV, respectively, while all patients from the control group maintained HBV-DNA. At 15 months of follow-up, 6 patients (33%) under therapy (2 from each group) and 1 from the control group remained HBV-DNA-negative. Knodell's index decreased significantly on comparing basal and final liver biopsies among patients in group IV (16.0 +/- 1.9 vs 7.0 +/- 1.9, p less than 0.01), while no changes were observed in the other groups. Five patients (27%) developed anti-IFN antibodies during treatment. In summary, although low doses of rIFN-alpha (2.5-5 MU) had an antiviral effect on HBV replication, only patients treated with 10 MU showed a significant decrease in liver histological activities. In addition, the effectiveness of rIFN-alpha therapy may be negatively influenced by the appearance of anti-IFN antibodies.