To evaluate the prognosis of the interferon (IFN)-treated patients with chronic hepatitis C (CH (C)), the clinical course and outcome of patients with CH (C) who were administered IFN more than 5 years before was compared with the natural course of untreated patients with CH (C) who were followed-up for 5 years. Good responders to IFN therapy showed normalized serum ALT level thereafter except one patient who were positive for serum HCV-RNA and had relapse of hepatitis. Histological improvements were observed in good responders. In groups of poor responders and non-responders, the fluctuation of serum ALT and histological changes after IFN therapy seemed to be similar to the natural course. Several problems on the prognosis are discussed.