Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline–regulated expression of viral structural and nonstructural proteins. These well–characterized inducible cell lines were found to efficiently process and present endogenously synthesized HCV proteins via MHC class I. Functional MHC class I cell–surface expression and intracellular proteasome activity were not affected by the expression of HCV proteins. These results suggest that viral evasion of the host immune response does not involve interactions of HCV with MHC class I processing and presentation. Other mechanisms, such as interference with the interferon system, may be operative in HCV infection, leading to viral persistence. (Hepatology 2001;33:1282–1287.)