The neurotoxic potential of cyclosporine in previous clinical experience has not been considered a significant problem. Recently a significant incidence of severe neurotoxicity has been related to cyclosporine therapy in liver transplant recipients. In our heart transplant program we have observed an unexpectedly high incidence of serious neurologic toxicity, presumably caused by use of cyclosporine. Coma, cerebral hemorrhage, hemiparesis and dysphasia, confusion, and visual hallucinations were reported in four patients. Cyclosporine discontinuation or dose reduction eliminated the neurologic effects in all but one patient. Cyclosporine neurotoxic effects should be suspected in heart transplant recipients with central nervous system syndromes.