The aim of this study was to evaluate the impact of mycophenolate mofetil (MMF) on incidence, delay, severity and clinical course of early recurrent hepatitis C after liver transplantation (LT). A total of 21 hepatitis C virus (HCV)-positive patients after LT were prospectively enrolled in this study. All of them received a quadruple induction cyclosporine A (CsA)-based immunosuppression, augmented by MMF (n=12) or by azathioprine (n=9, AZA). MMF tended to delay recurrent disease (50+/-35 versus 35+/-35 weeks, P=0.5) with significantly lower levels of aminotransferases (P<0.05). Furthermore, patients under MMF revealed less severe allograft fibrosis at disease recurrence (stage of fibrosis: 1.5+/-0.5 versus 2.2+/-1.2; P=0.07). But stage of fibrosis significantly increased in the MMF-group (P<0.05) during 6 months of antiviral treatment. Three patients in the MMF-group and none of the controls suffered from severe fibrosing cholestatic recurrent hepatitis C. Initial post-LT administration of MMF tended to delay recurrent hepatitis C and to limit initial HCV-related biochemical and morphological graft dysfunction. But during clinical follow-up, its immunosuppressive capabilities exceeded possible antiviral properties, finally leading to significant progression of graft fibrosis. Thus, concomitant dose reduction of other basic immunosuppressants might be useful in this clinical setting.