Effects of interferon (IFN) treatment on 91 patients with chronic HCV-related liver diseases in three hospitals were analyzed. HCV-RNA encoding the NS5 region of HCV was detected by the RT-PCR method, and HCV genotyping was performed by slot-blot hybridization using the type-specific cDNA probes on HCV-NS5. HCV titers in blood before treatment with IFN were determined by the multicyclic PCR method. HCV-NS5 was positive in 61 out of 91 patients and the HCV-K1 genotype was found in 40 patients, whereas the HCV-K2 genotype was found in 21. To summarize results from all three hospitals, 52.3% of patients recovered completely and 33.3% recovered partially in the K2 group, in each of these the percentage was significantly higher than in the K1 group. In addition, the percentage of the patients showing no response to IFN treatment was significantly higher in the K1 group than in the K2 group. In the HCV-NS5-negative group, the percentage of patients who did not respond was significantly lower than in the K1 group. In the K1 group, a complete recovery tended to be found more frequently in patients with lower titers of HCV. However, some patients with low titers of HCV did not respond to treatment. The differences of HCV titers between the groups showing different responses to IFN treatment was not statistically significant. In the K2 group, HCV titers were significantly lower than those in the K1 group; however, the effects of IFN were not related to the titers of HCV in K2 group. Two patients with liver cirrhosis in the K2 group had a complete or partial recovery, whereas four patients with liver cirrhosis in the K1 group did not respond to IFN treatment. These results indicate that the HCV genotype is the most important determinant of the effects of IFN treatment.