Mathematical modeling of viral dynamics reveals high turnover rates of pretreatment viral production and clearance (10(11)-10(13) virions/day) and permits the estimation of in-vivo half-lives of a few hours for HCV free virions. The balance between virus production and clearance in untreated patients with chronic hepatitis C virus results in a decline of viremia when active antiviral treatment is initiated. During the first phase of IFN-alpha therapy, the kinetics of the viral load is characterized by a rapid, dose-dependent decline. After about 24 to 48 hours, the viral decline enters a second phase of a relatively slow exponential decay during the following weeks of therapy which may reflect the death rate of infected hepatocytes. The second-phase decay is predictive for the virologic end-of-treatment status and, even more so, for the likelihood of sustained response. Nonresponding patients typically show constant viremia or even a rebound during this second phase.