BACKGROUND Hepatitis C virus (HCV) infection is prevalent among renal transplant recipients. METHODS Twenty-five recipients of living donor renal transplantation with HCV (group I) and without HCV (group II) were serially monitored at three time points, that is, pretransplant, day 10, and 6 months posttransplant. Phenotypic characterization of T-cell subsets and natural killer cells was performed by flow cytometric immunophenotyping. Cytometric bead array immunoassay was used to simultaneously measure six cytokines (interleukin [IL]-2, IL-4, IL-5, IL-10, tumor necrosis factor-α, and interferon-γ) from phytohemagglutin-stimulated culture supernatants, and transforming growth factor (TGF)-β1 levels were determined by ELISA. Real-time polymerase chain reaction method was used to determine the serum viral load among group I patients at three time points. RESULTS Group I patients on day 10 posttransplant showed a significant increase in T cells subsets with reduced interferon-γ and increased TGF-β1 levels. A significantly increased CD8 T cells and TGF-β levels were seen at 6-month posttransplant among group I patients. Multivariate linear regression analysis showed TGF-β and tumor necrosis factor-α as the most significant predictors affecting early (day 10) and late (6 months) posttransplant viral load, respectively. CONCLUSIONS After an initial increase in the viral load immediately posttransplantation, there is a reduction in viral load. A concomitant timed dissection of the immune response shows a complex interactive environment in which, despite immunosuppression, not only the antiviral immune response persists but the virus is also able to modulate the host immune response for its survival. Per se, HCV does not adversely affect the allograft or patient outcome in this case-control study.