Fatal leucoencephalopathy is a rare calcineurin inhibitor-related complication, especially in kidney and liver transplant recipients. The only means of clinical management reported so far is the discontinuation or reduction in the calcineurin inhibitor. We herein report a case of a 37-yr-old male who developed leucoencephalopathy 12 wk after heart transplantation and recovered after stabilization of metabolism and arterial blood pressure. The findings in this case support the hypothesis that tacrolimus-associated neurotoxicity is severely increased by an impairment of the blood-brain barrier. Withdrawal of tacrolimus was not necessary while other causes of endothelial injury were treated successfully.