Responses of patients infected with chronic hepatitis C virus (HCV) to interferon-alpha (IFN-alpha) treatment were studied. HCV genotypes were determined by molecular and serologic techniques. Levels of HCV viremia were determined by quantitative reverse transcription-polymerase chain reaction. Infection with HCV genotype 2 or low pretreatment HCV viremia levels in subjects infected with genotype 1 were associated with favorable (complete and sustained) responses (CR-SR; P < .001) to IFN-alpha treatment. HCV viremia levels in genotype 2 infection were significantly lower (P < .05) than in genotype 1 infection. The reduction rates of serum HCV RNA levels were four times higher in patients with genotype 2 infection than in those infected with genotype 1. The proportion of patients with CR-SR who experienced virologic relapse after completion of IFN-alpha treatment was higher for those infected with genotype 1. The proportion of patients with CR-SR and genotype 1 infection increased linearly in accordance with increases in single or total IFN-alpha dose.