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The availability of islet transplantation is limited by both the number of donor pancreata and the number of islets required for successful transplantation. There is evidence that the liver presents a less than optimal environment for islets that contributes to short- and long-term beta cell destruction or failure.It is our hypothesis that the pancreas is a suitable transplant site and may require fewer islets than standard sites such as the liver or kidney, and could lead to improvements in transplantation outcomes.To test this hypothesis both a rodent and a canine model were used. Syngeneic rat islets were transplanted to the pancreas, liver, or kidney of Lewis rats. Fasting blood glucose levels were compared for three months as an index of islet function. Dogs received an islet autotransplant to a pancreatic remnant. Insulin and glucose concentrations were followed for six months.In the rat, normoglycemia was maintained with 600 islets transplanted in the pancreas in contrast to the liver (3,200 islets) or kidney (1,000-2,000 islets). Dogs remained normoglycemic after receiving an intra-pancreatic islet transplant (mean 7,640+/-3,600 islets). There was no evidence of pancreatitis or nutritional deficiency in either species.The pancreas should be considered as an islet transplant site. The pancreas is the native milieu for islets, and offers the advantage of requiring fewer islets than other conventional sites, thereby increasing the possibility that one donor pancreas may serve one or more recipients.