The most consistently identified predictive factors for a response to both IFN-alpha monotherapy and IFN-alpha in combination with ribavirin are a low HCV RNA level, the absence of fibrosis, infection with HCV genotype 2 and 3, and a prolonged duration of treatment. In addition, an early response to IFN-alpha predicts response to IFN-alpha monotherapy but not necessarily to combination therapy. There does not appear to be any major gain in treating IFN-naive patients with HCV genotype 2 or 3 infection with a combination of IFN-alpha and ribavirin for longer than 6 months. The identification of these predictive factors has allowed improvement in study design and assessment and may provide a patient with an idea of the likelihood of response, making possible a more informed decision regarding treatment. At present, none of these factors, either alone or in combination, completely predicts response to IFN-alpha. Thus, individual patients should not be denied treatment on the basis of these factors.