The invention rates to a hepatitis C virus (HCV) cDNA-based culture system capable of synthesis of infectious HCV in cell culture and cell-to-cell spread of the virus. The invention also relates to a method of measuring the level of HCV infection in a hepatocyte cell. A method for identifying a modulator of HCV activity is also presented, and a method for modulating HCV activity. The invention provides a reliable system for both genetic analysis of the viral genome and for the development of novel antiviral strategies.