Pancreas transplantation, when successful, is a reproducibly effective method to normalize glycemia without the use of exogenous insulin treatment in patients with diabetes mellitus. Success rates for combined pancreas and kidney transplantation are ~70%, and patient survival rates are ~90% 1 yr postoperatively. Metabolic benefits of this procedure include normalization of levels of fasting plasma glucose and HbA(1c). Glucose-induced insulin secretion and intravenous glucose tolerance are normalized. Improvements are also observed in glucose recovery after insulin-induced hypoglycemia and in glucagon secretion during hypoglycemia. Pancreas transplantation is also associated with normalization of kidney structure and both motor and sensory nerve function. However, no benefits have been observed with regard to pancreatic polypeptide secretion, kidney function, and the retinal pathology of diabetes mellitus. Pancreas transplantation has reached a point in its history where the operative technique and its ancillary medical therapy have been optimized. Improvement in the rates of success, morbidity, and mortality will probably depend on improvement in immunosuppressive drugs and the physical condition of the recipients themselves. The time is at hand when we need to carefully consider whether it is ethical and advisable to make pancreas transplantation available to individuals who have fewer chronic complications of diabetes mellitus. Future studies of pancreas transplantation must incorporate more rigid experimental controls than have been used in the past to better assess the relative merits of this procedure.