Neurotoxicity associated with calcineurin inhibitors cyclosporin A and tacrolimus is established. Sirolimus is a new agent related to tacrolimus, but its mechanism of action differs. The authors reviewed 202 transplant recipients treated with sirolimus from 2001 to 2004. They found no evidence of neurotoxicity with sirolimus therapy for up to 18 months (range, 15 days to 3 years). Sirolimus could be considered a substitute immunosuppressant for patients with cyclosporin A or tacrolimus neurotoxicity. The authors reviewed 202 transplant recipients treated with sirolimus from 2001 to 2004. They found no evidence of neurotoxicity with sirolimus Sirolimus could be considered a substitute immunosuppressant for patients with cyclosporin A or tacrolimus neurotoxicity.