Background. Reverse transcriptase polymerase chain reaction (RT-PCR) can detect the viral genome and show hepatitis C recurrence in patients who undergo transplantation for chronic hepatitis C viral (HCV) infection. We investigated the utility of an RT-PCR-based HCV assay for early detection of viral RNA in de novo HCV infection after liver transplantation. Methods. Pretransplantation antibodies and explantation HCV viral RNA status were obtained from 117 patients. Follow-up liver biopsy specimens were examined for evidence of hepatitis activity. Plasma samples during the period of time of the biopsy were assayed for HCV antibody and viral RNA. RNA was extracted from samples and reverse transcribed to cDNA. cDNA was amplified by PCR, and products were detected by liquid hybridization. Results. Clinical hepatitis developed in seventeen of 117 patients who, before transplantation, were HCV antibody negative and explant viral RNA negative. Ten patients were plasma PCR negative and had known non-hepatitis C causes for the biopsy findings. Of the remaining seven patients, five (70%) were plasma RT-PCR positive before seroconversion in matched plasma samples. Conclusions. In liver transplant patients, the incidence of de novo clinical hepatitis is low, and HCV viral RNA in de novo clinical hepatitis C infection can be detected in the absence of HCV antibodies.