High liver enzymes (HLE) as a metabolic consequence of sirolimus therapy has been encountered in various studies, however its incidence did not exceed 20%. The impact of sirolimus on liver function among hepatitis C virus infected renal transplant patients awaits in depth evaluation. This study was carried out between May 2001 through June 2002 including 80 live–donor renal allotransplant recipients. The patients were stratified into 2 equal demographically matched groups to receive either sirolimus (5 mg) + steroids + low dose tacrolimus (Group A) or sirolimus (10 mg) + steroids + mycophenolate mofetil (Group B). Both groups received basiliximab induction therapy. Follow up of all patients was carried out (mean 18.13_+5.19 months). Routine biochemical assessment of liver function was carried out for all patients in addition to hepatitis C viral assay. The prevalence of HCV infection was 37.5% and 50% in group A and B respectively. High incidence of HLE cases was encountered among our patients being 47.5% and 57.5% in group A and B respectively. No significant difference was found between either group regarding the severity and duration of elevated transaminases in spite of different sirolimus doses. Statistically significant higher levels of ALT and AST were encountered among HCV positive patients (mean ALT= 437.7 ± 417 in HCV+ve & 186.8±84 in HCV –VE patients, P =0.011). The administration of sirolimus as a part of immunosuppression in HCV positive renal transplants may be associated with significant elevation of hepatic enzymes. Temporary reduction of sirolimus dose with or without ribavirin therapy could be tried in such cases.