The source of the new islets during growth and the effect of aging on the number of islets have been studied in Webster Swiss mice. A combination of methods was employed, including microscopy in vivo, enumeration of the total number of islets, radioautography with H-3-thymidine, and conventional histological technics. The total number of islets in normal mice increases with age until about six months, and then becomes stable or decreases slightly. Radioautographs showed that the cells of the islets are in all likelihood derived from migrating ductal or periductal cells residing at the junction between the islet and pancreatic duct and at the periphery of the islet, and that these cells doubtless serve as the progenitor pool for the growth of the islet. The nuclear cycle of the insular cells was also determined by this method. In vivo study revealed that the structural integrity of ducts and of their vascular supply is important for the maintenance of the population of ductal and periductal islets. DIABETES 75:480-91, July, 1966.Regeneration of pancreatic tissue and formation of new islets of Langerhans in adult mammals of various species have been described in a variety of experimental conditions, including partial or complete pancreatectomy, 1 " 7 ligation of the pancreatic duct, 8 ' 9 ligation of the pancreatic arteries, 10 prolonged hyperglycemia produced by intravenous infusion of glucose, 11 protracted glucagon administration, 12 force-feeding of a high carbohydrate diet 13 and the administration of alloxan. 14 " 16 Whether new islets of Langerhans are formed in the resting pancreas of adult mammals under normal conditions is disputed, 7 " 22 and information concerning the formation of islets in aging is scanty.In both the experimental and the normal state, the