Diabetes mellitus is the leading cause of end-stage renal disease in the United States. Renal transplantation is currently the treatment of choice for diabetic patients on renal replacement therapy. Current immunosuppression includes medications that are diabetogenic and place nondiabetic transplant recipients at risk for developing posttransplant diabetes mellitus and subsequent de novo diabetic nephropathy in the allograft. Here we present three patients who underwent a deceased donor renal transplant and developed posttransplant diabetes mellitus. In all three patients despite excellent glycemic control (HbA(1c) < or = 7%) and average tacrolimus trough levels less than 10 ng/ml, clinical and histologic de novo diabetic nephropathy developed within 2 years of the diagnosis of posttransplant diabetes mellitus. This is in contrast to other reported data in which the average time to onset of de novo diabetic nephropathy was approximately 10 years. Additionally, in other case series the average HbA(1c) was 8.4% in patients who developed diabetic nephropathy. It is possible that the metabolic milieu of transplant recipients warrants tighter glycemic control. The allograft is also susceptible to hyperfiltration injury which may accelerate the diabetic lesions even at normal glucose levels. Further studies are warranted to determine the optimum glycemic control in posttransplant diabetes mellitus.