Hepatitis C virus infection causes acute and often chronic hepatitis. Therapy with interferon-alpha has been shown to induce remission of the inflammatory process within the liver and also elimination of the virus. However, only about 50% of treated patients respond in terms of at least a transient disappearance of viral RNA from the circulation below the limit of detection. In order to find prognostic factors for responsiveness, patients with chronic hepatitis C virus infection were analyzed for virus genotype and pretreatment biochemical liver parameters including serum AST, ALT, and gamma-GT activities. Whereas the initial biochemical response to interferon-alpha 2a was found not to be related to virus genotype, the initial virological response was found to be closely related to infection by genotype 3a and to a low pretreatment ratio of serum gamma-GT/ALT activity. These data confirm and extend the importance of virus genotype for responsiveness to interferon-alpha therapy and introduce an additional, host-specific parameter with a potential predictive value, namely the pretreatment ratio of serum gamma-GT/ALT activity.