OBJECTIVE A randomized controlled trial was set up to assess the effect of two different therapy regimens with lymphoblastoid interferon on the treatment and follow-up of patients with chronic C hepatitis. METHODS Eighty-five patients with chronic hepatitis C were randomized into two treatment groups (n = 30 respectively) and one control group (no treatment: n = 25). In one treatment group patients received three million units of alpha-lymphoblastoid interferon. The other received six million units. RESULTS A rapid decline in both alanine aminotransferase and aspartataminotransferase levels was seen in most treated patients (a complete response in 51% from group A and 55% from group B; partial response 29% from group A, 25% from group B). In five partial responders and six complete responders from group A and in seven partial responders and six complete responders in group B serum aminotransferase levels returned to baseline values in the follow-up. No change in serum bilirubin, albumin, IgG and prothrombin time during interferon treatment were seen. The histologic staging remained unchanged throughout the entire study. CONCLUSIONS alpha-interferon treatment improves the clinical picture, biochemical parameters and histologic pattern in a large percentage of patients with hepatitis C. Long-term remission was seen in only 37% of treated patients. Using six million units of alpha-interferon has not proven to be significantly better than three million units. Protracted treatment for nine months seems to increase the percentage of patients in biochemical and histologic remission.