Between January 1996 and February 1999 we treated two groups of patients with chronic hepatitis C and HCV genotype 1 according to different treatment regimens. 29 patients in group were treated in a prospective, open trial and received an initial dose of 6 MU Interferon-alpha-2a daily. In case of virologic response within the first 12 weeks of treatment a dosage reduction to 6 MU three times weekly was performed until the end of week 12 and 3 MU three times weekly thereafter until the completion of month 12. 35 patients in group 2 received 5 MU (Interferon-alpha-2b) or 6 MU (Interferon-alpha-2a) three times a week. If serum HCV RNA was negative after three months of treatment patients received 3 MU thrice weekly until completion of month 12. This regimen was considered standard therapy at the time of treatment. In both groups therapy was stopped in patients in whom HCV RNA remained detectable after 12 weeks of treatment or in patients who underwent virological breakthrough. The end point was a sustained virologic response defined as the absence of serum HCV RNA 6 months after treatment was completed. Primary response rates as defined by negative serum HCV RNA within the first 12 weeks of treatment were 59% in group 1 and 17% in group 2. Sustained response rates were 10% in group 1 and 3% in group 2. Initial daily dosing as in group 1 was therefore not associated with a higher sustained response rate compared to standard therapy. The safety profile was in accordance with the known side effects of interferon-alpha and was comparable in both treatment groups.