Patients with chronic hepatitis C, with a high serum viral load (≥ 1 Meq/ml) and genotype 1b seem to be resistant to interferon (IFN) therapy. To evaluate the efficacy of a Kampo herbal medicine (Mao-to) in combination with natural IFN-β for the treatment of these patients, 18 Japanese patients were enrolled in this study. Every patient received 6 million units (MU) of IFN-β intravenously daily for 8 weeks. Mao-te was given orally three or four times a day during the IFN-β administration. Of the 18 patients, 16 became negative for serum hepatitis C virus (HCV) RNA at the end of treatment, but only two of them (11%) remained negative for the virus RNA at 6-month follow-up. Serum alanine transaminase (ALT) levels normalised in 17 patients (94%) at 2 weeks of follow-up after the cessation of therapy, and 11 patients (61%) retained normal ALT levels for more than 6 months of follow-up. This rate of biochemical response was high compared with that of therapy with IFN-β alone (19%) in the largest IFN-β trial in Japan. Serum hyaluronic acid levels were decreased significantly from 147.0 ± 110.5 ng/ml to 77.4 ± 67.4 ng/ml in the sustained biochemical response group.