The efficacy of different doses and administration periods of interferon (IFN)-alpha treatment for patients with chronic hepatitis C was retrospectively evaluated by using the return of serum alanine aminotransferase (ALT) to normal levels 12 months after therapy as an index. Two hundred forty-one patients with chronic hepatitis C received 6 to 9 mega units of IFN-alpha once, twice, or three times per week for a different number of weeks. ALT levels generally returned to normal in 77 of the 241 patients (32.0%). The efficacy of IFN-alpha therapy with a total dose of 350 mega units or more was significantly superior to that with 350 mega units or less (30 to 45%, p < 0.05). However, the efficacy was the same if a total dose was more than 350 mega units, and more than 700 mega units did not improve the response rate. Administration periods of more than 6 months and less than 1 year appeared to be the most effective in this study. To achieve a complete response, administration three times a week was better than once a week. The higher the dose administered within a certain period, the higher was the efficacy of the IFN-alpha treatment. However, the factors affecting response must be further studied, because there are patients who respond to therapy with a total of only about 200 mega units, and patients who do not respond even to 800 mega units given for more than 1 year.