In this study the endocrine function following intraperitoneal hetero- and orthotopic pancreatico-duodenal-splenic allotransplantation (PDS) in hemipancreatectomized, non-immune-suppressed chacma baboons was assessed. Significantly reduced K-values and insulin release together with glucose intolerance during IVGTT were observed in hemipancreatectomized recipients (HPS) without grafts. Orthotopic and heterotopic PDS transplantation improved the glucose intolerance of HPS recipients; orthotopically sited grafts rendering the best curves. Normal glucose tolerance was not achieved. Both orthotopic and heterotopic PDS transplantation rendered suboptimal insulin release during IVGTT; heterotopically draining grafts released significantly more insulin than orthotopic grafts. Hyperglucagonaemia during IVGTT was a constant feature in both groups, heterotopic grafts releasing the most glucagon during stimulation. C-peptide release was significantly lower in orthotopic grafts compared to normal animals or heterotopically drained insulin. It is concluded that glucose tolerance was not directly related to insulin or glucagon release in this study as orthotopic grafts rendered near-normal IVGTT curves in the presence of hypoinsulinaemia, hyperglucagonaemia, and reduced C-peptide values. The hormonal response after PDS transplantation was variable and the advantages of portal vs systemic insulin drainage remain to be defined.