After heterotopic pancreatic allotransplantation in dogs and in the absence of rejection there was a fasting normoglycemia with a marked hyperinsulinemia. On i.v. glucose tolerance testing and i.v. glucagon testing, the blood sugar response of dogs receiving no immunosuppression was normal but the response in dogs receiving immunosuppressive therapy was exaggerated. There was a marked increase in the insulin [I] response compared with normal animals whether or not immunosuppressive therapy was administered. The 1st endocrine event during allograft rejection seemed to be a drop in the pancreatic I reserve as demonstrated by plasma I results during a glucagon test, occurring 2-3 days before clinically overt rejection. This was found on glucose tolerance testing. A rise in the fasting plasma I occurred next, 1-2 days before a rise in the fasting blood sugar. As the rejection process progressed, the plasma I levels subsequent dropped until the animal death. If, during a rejection process, the blood sugar did not rise above 150 mg/100 ml and the plasma I level did not drop below the lower normal limit the rejection was usually reversible with i.v. methylprednisolone.