We report the case of a 41-year old patient who underwent orthotopic liver transplantation because of decompensated liver cirrhosis due to chronic HCV-infection. Severe acute allograft rejection was insufficiently controlled by cyclosporine A, steroids and a 6-day regimen of OKT 3 monoclonal antibody therapy. As a consequence immunosuppressive therapy was switched to FK 506 in a dose of 3 mg bid. The FK 506 concentration in whole blood consistently ranged between 5.1 and 7.8 ng/ml. Seven weeks after the onset of FK 506 therapy the patient developed severe diabetes mellitus with fasting blood glucose levels up to 640 mmol/l. The C-peptide was elevated reflecting a higher than normal insulin secretion. Intravenous insulin therapy with application of up to 85 units regular insulin per day was initiated. Because of the severe diabetes immunosuppression was changed back to cyclosporine A. After six weeks the patient did no longer require insulin and showed an entirely normal glucose tolerance test, C-peptide and Hb A1-level. This case shows that the diabetogenic side effect of FK 506 is more pronounced than that of cyclosporine A. We propose to change immunosuppressive therapy to cyclosporine A in cases of FK 506 induced severe diabetes mellitus, since long-term prognosis of many transplant recipients may depend on side effects of the immunosuppressive agents.