Severe neurologic complications following treatment with cyclosporine are uncommon. They tend to occur during the first month of treatment and disappear after withdrawal or reduction of the dose of the drug. We report the case of a man who underwent a liver transplantation and subsequently developed severe central nervous system toxicity. After two years receiving cyclosporine, he presented with a brachial monoparesis and a complex visual disturbance. Symptoms slowly worsened during four months. On admission, he had confusion and seizures. Multiple areas of T2 prolongation, located in cerebral white matter, were seen on magnetic resonance imaging (MRI). Symptoms partially improved after cyclosporine withdrawal, but brain lesions shown on MRI persisted in serial imaging studies after two years of follow-up. We discuss the mechanisms that have been proposed to explain this clinical picture. Severe cyclosporine-associated neurotoxicity can also occur after chronic administration, even with serum levels in therapeutic range.