In clinical pancreas transplantation, duct-occluded segmental allografts are often used. There is concern that fibrosis following duct-occlusion may lead to progressive graft failure. In this study, sequential histology and endocrine function in long-term (up to 5 years) canine autografts were assessed. Segmental pancreatic autografts with residual pancreatectomy were performed, and the pancreatic duct was occluded with cyanoacrylate glue. Serial i.v. glucose tolerance tests (IVGTT) and percutaneous needle-core biopsies of the grafts were performed as long as grafts functioned. Ten dogs were long-term (greater than 18 months) survivors: 8 dogs had functioning grafts for a median of 48 months (range 18-60) after transplantation, and 3 dogs had graft failure at 21, 27, and 60 months. The mean 40-min blood glucose concentration (BGL-40') after i.v. glucose injection did not increase with time up to 5 years after grafting. Graft biopsies showed a universal picture of aggregated islet cells and fibrous replacement of acinar tissue. The total amount of fibrosis did not change with time, but the existing fibrosis became less cellular and more dense. This long-term study showed that in autografted animals, adequate endocrine function was maintained in the majority of cases, and progressive replacement of islet tissue by fibrosis could not be demonstrated in serial biopsies taken between 18 months and 5 years after autotransplantation. We therefore conclude, that while duct-occlusion results in extensive fibrosis, the process is not progressive, and although fibrosis may contribute to late graft failure this is not inevitable.