Neurotoxicity is a serious complication following orthotopic liver transplantation leading to increased morbidity and mortality. Neurotoxicity may be evoked by various perioperative factors, or may be due to drug-specific toxicity of immunosuppression. In the present study we evaluated the incidence of central nervous system (CNS) toxicity occurring within the early postoperative period of 121 patients, 61 randomly assigned to FK 506- and 60 to CsA-based immunosuppression as part of a multicentre study. The incidence of moderate or severe CNS toxicity was higher in patients treated with FK 506 (21.3%) than in patients receiving CsA (11.7%). The duration of symptoms was also greater in patients treated with FK 506 than in patients receiving CsA. The incidence of moderate or severe neurotoxicity after retransplantation was markedly greater in patients treated with FK 506 (100% of the patients).