Background/Aims: Serum HCV RNA was quantitated by the competitive polymerase chain reaction before, at the end of, and after interferon therapy, We assessed whether serum HCV RNA titer at the end of interferon therapy predicts the long-term outcome of treatment. Methods/Results: Of 71 patients treated with various doses of interferons, 21 became negative for HCV RNA persistently during follow up of 2 years, and they were considered as complete responders, The serial determinations of HCV RNA titer for each individual showed that in patients with HCV RNA negative at the end of therapy, the complete response rate was quite high (78.6%), while in patients with HCV RNA titer greater than or equal to 10(4) copies/ml at the end of therapy, none became complete responders in long-term follow up, The percentage decreasing to greater than or equal to 10(2) copies/ml of HCV RNA at termination of interferon tended to be higher in patients with genotype 2a (14/21, 66.7%) than in those with genotype Ib (18/42, 42.9%). The complete response rate of patients whose viral load was less than or equal to 10(2) copies/ml at termination of interferon was significantly higher in genotype 2a (11/14, 78.6%) than in genotype Ib (5/18, 27.8%) (p < 0.01), Pretreatment HCV RNA titer appeared to correlate to the titer at the end of therapy (r=0.596, p < 0.001); even when HCV RNA decreased to less than or equal to 10(2) copies/ml, the higher pretreatment titer indicated a lower likelihood of complete response (p < 0.05). Conclusions: These results indicate that HCV genotype and pretreatment viral titer are important factors in the response to interferon therapy, In addition, our study suggests that it is possible to stop interferon therapy at an appropriate time by monitoring HCV RNA titer.