Acute rejection is still a common complication of hepatic transplantation. The diagnosis, based on the histological examination of the graft, may be difficult to confirm in the setting of combined hepatitis C virus infection. The presence of C4d in the portal capillaries could facilitate differentiation between acute rejection and relapsed hepatitis C. The deposit of C4d provides evidence of activation of humoral immunity. To attempt to confirm this hypothesis, we searched for the presence of C4d in posttransplant hepatic biopsies.Thirty-six biopsies from 34 patients were analyzed retrospectively. The samples had been requested for one of the following reasons: suspected rejection, relapsed hepatitis C infection, or systematic check-up 1 year after the transplant.C4d expression was common in biopsies classified as acute rejection (33%) and chronic rejection (100%). C4d was never detected in the event of recurrent hepatitis C infection without rejection.These results, which are comparable to recently published data, give credence to the theory that C4d could be used as a marker for rejection following hepatic transplantation.