We studied tolerance to subcutaneous (s.c.) administration of 6 million units of interferon-beta (IFN-beta), given three times per week for 6 months, and its efficacy in the treatment of 15 patients with chronic hepatitis C. At the end of the treatment, alanine aminotransferase (ALT) levels were significantly reduced (p = 0.024) in all patients, and 4 (27%) had a normal ALT value. However, at the end of the study (12 months), only 1 of these 4 had a sustained response. No patient cleared hepatitis C virus (HCV) RNA completely, but the RNA could be detected only by polymerase chain reaction (PCR) in the sustained responder. Adverse side effects to the s.c. IFN-beta were infrequent. Leukocyte (p = 0.012) and platelet (p = 0.013) counts decreased significantly during treatment but did not necessitate dose modifications. Thus, although s.c. IFN-beta at the dosage used had little efficacy in the treatment of chronic hepatitis C, the excellent tolerance to the treatment suggests that the effects of higher doses should be explored.