Pancreatic endocrine function was studied in forty dogs after ligation or free i.p. drainage of the pancreatic duct, with or without simultaneous partial pancreatectomy. Shrinkage and fibrosis of the pancreas occurred in all dogs, with equal severity in the open duct and duct-tied groups. Fasting blood sugars remained within the normal range but fasting levels of plasma insulin and glucagon were reduced. Dynamic tests of endocrine function indicated that partial pancreatectomy reduced the insulin response to i.v. injection of dextrose or glucagon and delayed the reestablishment of glucose homeostasis. Glucose tolerance was normal in dogs with intact pancreases, but duct ligation was associated with deteriorating recovery after glucagon injection. The precise coordination of circulating glucose, insulin, and glucagon levels seen in normal dogs was lost in both partial and intact pancreas groups and these disturbances were attributed to the fibrotic changes arising from interference with the ductal drainage. Both ligation and free i.p. drainage of the pancreatic duct therefore resulted in abnormalities of islet function. When combined with partial pancreatectomy, both techniques were associated with significant pancreatic endocrine insufficiency.