Three sites were evaluated for potential pancreatic fragment autotransplantation. Both endocrine and exocrine functions were evaluated following autotransplantation into splenic pulp, portal vein, or hepatic parenchyma in 44 pancreatectomized dogs. Cholecystic bile amylase concentrations in the hepatic parenchyma group surviving more than 2 months were elevated significantly, and choledochal bile amylase concentrations increased markedly following pancreozymin-secretin injection. In contrast, bile amylase concentrations in dogs with intrasplenic or intraportal implants were low and did not respond to PS injection. Histologically pancreatic autografts in hepatic parenchyma revealed marked proliferation of exocrine tissue with abundant zymogen granules and reconstruction of the acinar lobules with a few islets. These acinar cells in the hepatic parenchyma were ultrastructurally normal. Transplant endocrine function, estimated by K values, was significantly better after splenic pulp and portal vein than after a hepatic parenchyma implantation, but no group improved during 1-year follow-up. Glucose-stimulated initial insulin responses were abnormally low in all recipients. Islet B cells lacked mature insulin granules, such as seen in normal resting B cells. This ultrastructural finding implies a persistent demand on the B cells and may explain the spontaneous recurrence of hyperglycemia and the diminished initial insulin response to a glucose load. This study indicates that euglycemic recipients of pancreatic fragment autotransplantation remain unstable and prediabetic.