Rapidly progressive and ultimately fatal liver failure with evolution to cirrhosis developed in a heart transplant recipient following infection by hepatitis C virus. Antiviral antibodies and the presence of viral RNA were analyzed throughout the course of the disease. After a weak initial response to a single viral epitope (c22-3), serology became negative, the infection remaining detectable by polymerase chain reaction only. This case demonstrates the potentially severe consequences of hepatitis C virus infection under immunosuppression. The incidence of this infection may be underestimated, as the presented case apparently would not have been detected if serology had been used for diagnosis.