Cyclosporine (CsA) is a widely used immunosuppressant following solid organ transplantation. CsA administration is associated with a number of systemic complications, including neurotoxicity. A 33-year-old man with cystic fibrosis, who underwent bilateral lung transplantation, presented with severe neurotoxic symptoms leading to coma in association with CsA administration combined with high doses of methylprednisolone for treatment of an acute rejection episode. After discontinuation of CsA, a quick resolution of his clinical status was observed, as well as of the pathological findings on magnetic resonance imaging (MRI). CsA was replaced with tacrolimus leading to an uneventful course.