In this study we compared the ability of perfused pancreases from 2 1/2 month-old and 12 month-old rats to secrete insulin in response to arginine or tolbutamide. The results indicate that the insulin secretory response to either secretagogue was between 25-85% greater (two-way analysis of variance, P less than .01) by perfused pancreases of older rats. On the other hand, islet cell mass was approximately three-fold greater in the pancreases of the older rats. When this difference in mass of insulin secretory tissue was taken into consideration, it became apparent that insulin secretion per beta cell by perfused pancreases of the older rats was only half that of the younger rats in response to either arginine or tolbutamide (two-way analysis of variance, P less than 0.001). Thus, the decline with age in the ability of the beta cell to secrete insulin, previously noted in response to glucose, involves other insulin secretagogues as well.