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Cyclosporin A (Cy A) was evaluated in dogs to assess its effectiveness in prolonging survival of allogeneic pancreatic islet tissue transplanted to the spleens of totally pancreatectomized mongrel dogs. Thirty-seven dogs were made diabetic by total pancreatectomy. Ten untreated pancreatectomized animals survived a mean (± SE) of 6.3 ± 0.9 days and died with mean (± SE) plasma glucose levels of 23.2 ± 2.7 mmol/liter. Dispersed pancreatic fragments, prepared by collagenase digestion without separation of exocrine and endocrine components, were directly implanted into the splenic pulp of 27 pancreatectomized dogs. Twelve dogs given auto-transplants became normoglycemic after 4.3 ± 0.5 days and remained so until killed at 60 days post-transplant, although normal glucose tolerance tests were not achieved. Eight nonimmunosuppressed dogs given allogeneic pancreatic fragments did not become normoglycemic but survived for 13.0 ± 2.1 days, the dogs dying with a terminal plasma glucose of 22.7 ± 2.2 mmol/liter. An additional seven dogs given allogeneic transplants were given Cy A (oral solution), 25 mg/kg/day, for 14 days, and, although failing to become normoglycemic, survived for 28.1 ± 5.4 days and died with terminal plasma glucose levels of 25.1 ± 0.6 mmol/liter. Intra-splenic complications included subcapsular hematomas, intrasplenic necrosis and cavitation, capsular perforations, and arteriolar thrombosis. The failure to achieve normoglycemia with allogeneic dispersed pancreatic tissue in dogs treated with Cy A and the complications associated with the implantation of the tissue in the spleen do not suggest that this approach is worthy of clinical trial.