Approximately 85% of acute cases of hepatitis C infection result in chronic hepatitis. Spontaneous clearance of hepatitis C virus has been thought to occur exclusively after acute infection and is associated with a robust cellular immune response. We describe here a case of a renal transplant recipient who acquired posttransplant hepatitis C virus infection with rapid histological progression but who subsequently experienced spontaneous viral clearance along with histological remission after removal of immunosuppression. Immunologic studies showed persistently strong cellular immune responses. This case underscores the importance of restoration of the immune system in the control of hepatitis C virus viremia and disease progression and the need to minimize or obviate immunosuppression in organ transplant recipients.