We propose to carry out related studies on the normal and pathological states of the endocrine pancreas, especially as they relate to diabetes mellitus in man and pancreatic tumors in experimental animals: (1) The notion that an autoimmune process plays a major, and perhaps the crucial, role in the etiology of insulin-dependent juvenile diabetes in man will be put to an experimental test. Thymus-derived lymphocytes specifically activated against pancreatic cells will be used to induce diabetes in the athymic nude mouse. These experiments will be designed to detemine unambiguously whether lymphocytes sensitized against latent antigens associated with the islet cells can, by themselves, induce a permanent diabetic state in otherwise normal animals. (2) By a combination of heterotransplantation techniques in nude mice and sustained specific physiological stimulus for the target cells, we will attempt to induce and establish insulin-secreting transplantable tumors of the pancreatic islet cells in experimental animals. Eventually, such a strategy might be applicable to human cells as well. Preliminary evidence already obtained in this laboratory suggests that both of these approaches are feasible. The athymic nude mouse provides the necessary and unique experimental model for these studies.