The failure of exogenous insulin to prevent the complications of diabetes has led to the search for another mode of therapy. Whole pancreas transplants have met with little success. The successful transplantation of isolated islets of Langerhans in the diabetic Lewis rat model has provided much hope for the eventual "cure" of diabetes mellitus. Our work has centered on the techniques of mass isolation of islets, utilizing the enzyme collagenase to digest islets free from acinar tissue. Functional studies on normal, diabetic, and transplanted rats are in progress, and improved techniques for viability assay are being evaluated. We are studying the short-term preservation of whole pancreas by pulsatile organ perfusion. Endocrine-exocrine interrelationships of the pancreas will be studied in normal, diabetic, and transplanted dogs, as well as in the perfused, isolated pancreas.