This study was designed to estimate the efficacy and safety of IFN-alpha in type B chronic active hepatitis patients. Thirty two cases were subcutaneously injected with IFN-alpha daily 3,000,000 units, three time a week for 12 weeks. The drug was administered while the patients were in the hospital for the first week, who were followed up after discharge once every month for four months. The follow-up continued for a maximum of 14 months depending on the conditions of the cases (mean +- SD: 7.3 +- 5.0 months). Twenty five cases, as a control group, were not treated with IFN-alpha and observed for 3 to 18 months (mean +- SD: 7.6 +- 3.4 months). The results were as follows. In the patients treated with IFN-alpha, disappearance of HBe antigen was observed in 9 of the 32 cases (28.1%), and anti-HBe appeared in 8 of 9 cases (8/32:25.0%). In the control group, disappearance of HBe antigen showed in 4 of 25 cases (16.0%). Of the 4 cases, one showed anti-HBe (1/25:4.0%). No significant difference of disappearance of HBe antigen between the two groups. Signifirant difference, however, was noted in the appearance of anti-HBe. Follow-up was made on serum HBV-DNA titer in 15 cases injected with IFN-alpha. The levels were lowest between two to three months in 12 cases, and in four months of the follow-up in one case. Five cases converted to negative, in all 5 cases HBe antigen disappeared. The seronegative ratio of the two groups showed no significant difference in family history of type B hepatitis, age, sex, histologic finding, initial HBV-DNA titer and aminotransferase level. The serum transferase level in the group with IFN-alpha treatment made a remarkable decrease after 4 weeks of treatmen. In control group, aminotransferase decreased but not significantly during follow-up. All patients treated with IFN-alpha complained of fever, myalgia and other minor side effects not serious as to require treatment. Thus this findings suggest that treatment of type B chronic active heaptitis patients with IFN-alpha 3,000,000 units daily, three times a week for 12 weeks appears to be a safe and relatively effective way.