BACKGROUND: The development of posttransplantation diabetes mellitus has a major impact on the quality of life and long-term outcome. METHODS: One hundred thirty-nine patients without known glucose metabolism abnormalities and treated with FK-506, methylprednisolone, and mycophenolate mofetil/azathioprine were analyzed for incidence of and risk factors for developing impaired fasting glycemia (IFG) and diabetes mellitus (DM). RESULTS: Using the American Diabetes Association criteria, 15% developed IFG and 32% developed DM in the first year after transplantation. High trough levels of FK-506 during the first month after transplantation (especially >15 ng/ml) and high body mass index (BMI) were significant risk factors for IFG or DM. Patients with (steroid-treated) acute rejections in addition to high trough levels of FK-506 were most prone to develop DM, whereas high BMI conferred risk of developing IFG. Patients with posttransplantation glycemic abnormalities also had higher levels of serum triglycerides at the time of transplantation, but they needed a lower dose of FK-506 to obtain higher trough levels of FK-506, suggesting metabolic differences already present before transplantation. The only risk factor retained for persistent IFG or DM beyond the first year was a higher number of trough levels of FK-506 >15 ng/ml during the first month after transplantation. CONCLUSIONS: Induction with an FK-506 based immunosuppressive regimen resulted in a high incidence of glucose metabolism disorders in renal transplantation recipients. Higher trough levels of FK-506 during the first month, acute rejections, and higher BMI were the most obvious risk factors.