Low doses of natural interferon-alpha (IFN-alpha) were administered to 29 consenting patients. These patients had abnormally high values of transaminases despite long-term glycyrrhizic acid product use, or had discontinued drug therapy due to adverse drug reactions. Efficacy, safety and QOL were examined. As a result, ALT values showed significant decreases in ITT analysis. Emergence of anti-IFN antibody was observed in only one patient. Although QOL did not improve significantly with SF-36 in ITT analysis, PPB analysis of patients that completed administration indicated significant improvement in two subscales (PF: physical functioning, BP: bodily pain). Administration was discontinued in 18 patients, with four due to adverse reactions. In conclusion, long-term low-dose administration of natural IFN-alpha for chronic hepatitis C is safe and effective in that it improves ALT values with rare appearance of IFN-neutralizing antibodies.