This study evaluates sirolimus in preserving renal function in 28 patients who developed renal insufficiency after liver transplantation. Patients with a creatinine level higher than 1.8 mg/ml were eligible for conversion. Of the 28 patients, 7 (25%) did not tolerate sirolimus, 6 (21%) progressed to end-stage renal disease (ESRD), and 14 (50%) have been maintained on sirolimus with stable renal function. The 28 patients overall had a decline in creatinine of 0.38 mg/dl (P = 0.029) at week 4, with a small increase by week 24. However, the subset of 14 patients who did not develop ESRD had a decline in creatinine that persisted to week 48. While the differences between those who developed ESRD and those with stable renal function were not statistically significant, the patients who developed ESRD had a higher creatinine at conversion (2.8 vs 2.3) and a lower creatinine clearance (36 vs 53 ml/min). Patients receiving sirolimus had a persistent rise in cholesterol (P < 0.05). The use of sirolimus to preserve renal function was limited by patients unable to tolerate drug- (25%) and patients who developed ESRD (21%). A subgroup of patients (50%) had an improvement in creatinine that persisted for 48 weeks.