Efficacy of 50-week administration of interferon-alfa 2a to 159 chronic hepatitis B patients with or without HBe-antigen was investigated. Patients received 1 to 9 MU/injection of interferon for 26 to 50 weeks. 24.7% (23/93) of HBe-antigen-positive patients became HBe-antigen-negative after 24-week treatment with interferon. Those who remained HBe-antigen-positive after 24-week interferon therapy received additional 26-week of interferon and 35.1% (13/37) turned to HBe-antigen-negative. Nornal serum ALT at 12 month after interferon therapy was observed in 56.6% (25/44) of HBe-antigen-negative patients, althouth sustained clearance of serum HBV DNA was obtained in only 4 cases. 18.9% (30/159) dropped out mainly due to adverse effects of interferon. Fifty-week interferon therapy seems to increase the response rate of CH-B, althouth the high prevalence of adverse effects should be considered especially among those who received high-dose interferon.