Chronic nephrotoxicity is one of the most serious side-effects of calcineurin inhibitor treatment and a factor in mortality and morbidity after liver transplantation. In our transplant centre, among patients who underwent a liver transplantation between January 1989 and December 2000, 14 liver graft recipients (6.86%) developed de novo severe renal dysfunction as defined by a serum creatinine concentration above 200 micromol/L. Renal biopsy was performed in nine cases and evidenced histological lesions compatible with chronic nephrotoxicity related to calcineurin inhibitor treatment. For nine patients, we report the results of a prospective non-randomized study consisting of cyclosporine or tacrolimus withdrawal associated with administration of mycophenolate mofetil or azathioprine. Despite this therapeutic modification, we did not observe a significant renal function improvement but on the other hand, there was no graft rejection.