We have treated 16 patients with chronic non-A, non-B hepatitis with short term (7-13 weeks) and long term (1 year) interferon. Sustained effect (normalization) of treatment was noted in all by long term treatment, where 7 of 8 with short term treatment showed flare-ups of transaminase after the therapy. In addition, negative turn of anti-HCV antibody was noted in 2 of 5 patients with long term treatment, whereas such change was noted in none of 6 anti-HCV antibody positive patients treated with short term treatment. These data suggest that long term interferon therapy may change natural course of chronic non-A, non-B hepatitis caused by HCV.