Thirty-three Swedish patients with chronic post-transfusion non-A, non-B hepatitis entered a randomized traial of interferon alfa-2b treatment (INTRON A, Schering-Plough Corporation) (3 million units, three times weekly, subcutaneously for 36 weeks). Twenty-two patients (67%) were reactive for antibodies against hepatitis C virus. Nineteen patients completed the course of therapy; 11 (58%) had a complete response with normalization of serum alanine aminotransferase levels, compared to none of the 12 controls (p < 0.001). Four treated patients with chronic active hepatitis were non-responders. Non-responders had a significantly higher mean body weight than responders (p < 0.05) and tended to have a longer duration of prior disease. During the 10-month follow-up period post treatment, 4/11 (36%) complete responders had a sustained response and three (75%) of these four were reactive for antibodies against hepatitis C virus, whereas 7/11 (64%) relapsed, of whom four (57%) were reactive for antibodies against hepatitis C virus. All patients who were treated again responded but relapsed once more after retreatment was stopped. We conclude that the majority of patients with chronic post-transfusion non-A, non-B hepatitis will respond to 9 months' interferon alfa-2b treatment, but that only one of three responders will have a sustained response 10 months post treatment. Reactivity for antibodies against hepatitis C virus is not predictive of the outcome of therapy.