The aim of this study was to determine whether diabetes could be ameliorated in totally pancreatectomized baboons by heterotopic intraperitoneal autotransplantation of the tail of the pancreas with the duct unligated. Twenty-five baboons were made diabetic by total pancreatectomy. Six untreated pancreatectomized animals survived a median of 5 days with mean (+/- SE) plasma glucose levels of 18 +/- 1.37 mmol/L and mean (+/- SE) potassium (K) values of 0.36 +/- 0.02% before death. Successful autotransplantation of the tail of the pancreas rendered pancreatectomized baboons consistently normoglycemic. Intravenous glucose tolerance tests performed 6 weeks after transplantation in 12 autograft recipients showed glucose intolerance in 12 of 14 recipients, and K values were significantly reduced to 1.03 +/- 0.015% (P less than 0.05). The K value of 40 normal baboons was 2.18 +/- 0.15. Histologic examination of successfully transplanted autografts of 12 animals at 6 weeks showed islets with intact beta and alpha cells, atrophy of the exocrine pancreas, graft fibrosis, and a cellular infiltration of the mononuclear type. The addition of a distal arteriovenous fistula to the graft did not reduce the incidence of graft vessel thrombosis, and all five animals died of hemorrhagic pancreatitis and venous thrombosis within 24 hours of transplantation.