Hepatocellular injury in renal transplant recipients with hepatitis C virus (HCV) infection remains unclear. The suppressed immune response, in combination with increased viremia levels, provides a unique setting for the study of a potential HCV-induced apoptotic process. Liver biopsy specimens from 59 HCV-infected renal transplant recipients were examined histologically. DNA fragmentation was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling assay, and the CD8 T-cell count was assessed immunohistochemically.A low apoptotic index (0-2.5) was observed in 31 cases, a moderate index (2.6-5) in 16, and a high index (>5) in 12. Apoptotic cell death correlated significantly with viremia because it was demonstrated by higher HCV-RNA levels in cases with a high number of apoptotic cells (odds ratio, 2.96; 95% confidence interval, 1.0-8.5; P = .04). No correlation was found between the apoptotic index and hepatitis necroinflammatory activity, CD8 cell count, fibrosis stage, immunosuppressive therapy, or genotype. In HCV-infected renal transplant recipients, apoptotic cell death seems to be associated with high viral load, thus providing indications of viral interference in the pathogenetic process.