The aim of the present study was to evaluate the effects of cyclosporin A (CyA) on the blood perfusion of the transplanted pancreas. For this purpose syngeneic pancreaticoduodenal transplantations were performed in Wistar-Furth rats. After nephrectomy the graft was anastomosed using a nonsuturing cuff technique to the left renal vessels. Beginning 7 days after transplantation and then continuing for 2 weeks, CyA (15 mg/kg body weight) or vehicle was given p.o. once daily, 6 days a week. The serum CyA concentrations were greater than 600 ng/ml at all points in time tested. Intraperitoneal glucose tolerance tests were normal in CyA-treated animals after 12 days, but the pancreatic insulin concentration was decreased to the same extent in the native and transplanted pancreas. A microsphere technique was used to measure the blood perfusion of the pancreaticoduodenal graft, the native pancreas and duodenum, and remaining kidney 14 days after starting the CyA treatment. The renal blood flow was markedly decreased by CyA when compared with the control animals. In rats given vehicle alone, pancreatic, islet, and duodenal blood flows were higher in the graft than in the corresponding native organs. However, in rats given CyA, hyperperfusion of the graft was not observed. We conclude that the administration of CyA prevents the transplantation-induced blood flow increase seen in pancreaticoduodenal grafts of vehicle-treated rats. These observations may reflect graft denervation.