Within the multicenter European FK506 (tacrolimus) liver study, patients who received transplants for fulminant hepatic failure (FHF) were stratified separately from those having an elective transplant procedure. At 2-year follow-up, in addition to a comparison of the outcome between these two clinical groups, we report the efficacy and safety of tacrolimus primary immunosuppression (n=32) as compared with a cyclosporine-based regimen (n=23) in FHF. The FHF patients experienced more episodes of acute rejection and sepsis with reduced patient and graft survival rates compared with the elective group (e.g., retransplantation rate of 10/44 [22.7%] vs. 47/485 [9.7%], respectively). Among the FHF patients, tacrolimus reduced the actuarial incidence of acute rejection compared with patients treated with cyclosporine, and whereas refractory acute and chronic rejection occurred in four (17.4%) and two patients (8.7%), respectively, treated with cyclosporine, no rejection episodes were recorded in patients receiving tacrolimus. No difference in the actuarial patient or graft survival rates was observed between the two groups. Patients treated with tacrolimus tended to have a lower incidence of infection (pneumonia, 19.0% vs. 26.1%; cytomegalovirus infection, 9.5% vs. 26.1%; and sepsis, 23.8% vs. 39.1%). Corticosteroid dosage requirements were reduced in the tacrolimus-treated group with the cumulative dosage exposure from 20.8% to 37.2% lower on a monthly basis. No significant differences in adverse events attributable to the immunosuppressive drugs were found.