This retrospective study illustrates the efficacy of tracrolimus-based immunosuppression following simultaneous kidney and pancreas transplantation. Between March 1995 and December 1996, 24 simultaneous kidney and pancreas transplant recipients received tacrolimus-based maintenance immunosuppression. All patients received sequential therapy with an antilymphocyte agent, azathioprine, prednisone and tacrolimus. The dose of tacrolimus was adjusted to achieve a whole blood trough level of 8-15 ng/mL (IMx). The mean follow-up was 25 months with a median of 26 months (range 12-33 months). A rise in serum creatinine of > 20% over baseline was investigated with a renal biopsy, after mechanical causes for renal dysfunction had been excluded. Mean serum creatinine concentrations at 3, 6, 12, 18 and 24 months post-transplantation were 1.1, 1.2, 1.3, 1.3 and 1.3 mg/dL respectively. The blood glucose concentrations at the corresponding time period were 115, 94, 95, 93 and 95 mg/dL. Four pancreas allografts were lost (three in the immediate post-transplant period due to thrombosis, and one following iliac artery repair for aneurysm). Transient hyperglycemia requiring treatment was seen in 3 patients. There were four (17%) acute rejection episodes--one of the pancreas allograft alone and three involving the kidney. At a mean follow-up of 25 months, the patient survival and renal allograft survival were 100%, with pancreas allograft survival rate of 78.4% (Kaplan-Meier analysis). Nine (37.5%) patients had evidence of tacrolimus toxicity on renal histology. In conclusion, tacrolimus-based maintenance immunosuppression is associated with stable renal and pancreas allograft function, with freedom from acute rejection in 83% of patients.