Long-term side effects of immunosuppressive therapy with calcineurin inhibitors (CNI) in liver transplant (LT) patients are major causes of morbidity. We undertook a prospective study to assess the safety and efficacy of CNI withdrawal and replacement by mycophenolate mofetil (MMF). Thirty-three patients with a minimum follow-up of 2 years after LT were included in the study. They were all on monotherapy. Of these 30 had renal dysfunction attributable to CNI toxicity and 3 had hyperlipidaemia. Ten had both renal dysfunction and hyperlipidaemia. Twenty of these patients had also arterial hypertension. Renal function, blood pressure and lipid profile were measured before and 12 months after study entry. A sequential renal scintigraphy was also performed in every patients before and 12 months after study entry, to appraise renal damage and possible improvement. Side effects of medication and graft function were recorded during the study. At the end of the study there was a significant decrease in serum creatinine (by 28%) and urea levels (by 36%). Blood pressure improved significantly with a systolic decrease of 20% and diastolic decrease of 12%. There was also an improvement of cholesterol (by 21%) and triglycerides (by 56%). MMF was well tolerated by all patients. No episodes of active graft rejection occurred during the conversion period and when on MMF monotherapy. Substitution of CNI by mycophenolate mofetil can improve renal function, blood pressure and cholesterol and triglyceride concentration of liver transplant patients without an increased rejection risk with mycophenolate mofetil monotherapy.