The goal of this project is to develop a practical method for the treatment of Type I (insulin-deficient) diabetes mellitus in humans by transplantation of the fetal pancreas. A rat model system has been developed in which a single fetal rat pancreas can completely reverse streptozotocin-induced diabetes. Permanent storage of the fetal pancreas by cryopreservation has been developed. Rejection of allografts has been decreased by treatment of recipients with donor antigens plus short-term immunosuppression with procarbazine and antilymphocyte serum or alternatively with total lymphoid irradiation plus bone marrow or liver-cell transplantation. Preliminary results suggest that collagenase digestion and tissue culture of the pancreas prior to transplantation can decrease or prevent allograft rejection. This proposal is to carry out investigation of the human fetal pancreas which will be necessary prior to initiation of human transplantation. The developmental biology will be studied to determine the optimal stage for function as a donor organ. Methods to select optimal donor-recipient combination include blood and tissue typing and MLC of donor and recipient lymphocytes. Cryopreservation of donor tissues and cells will be established and a bank of cryopreserved tissues will be developed. Methods for alleviating or preventing rejection will include treatment of donor pancreases by digestion and tissue culture.