The action of fructose on insulin secretion was studied using isolated perfused rat pancreas preparations. It was found that fructose potentiation of insulin release occurred when a stimulatory concentration of glucose was also present. However, when glucose was absent from the perfusing medium, fructose alone did not result in the release of insulin. Also, cycloheximide greatly diminished this observed fructose potentiation of glucose—induced insulin secretion. This suggests that the fructose effect may be involved in the biosynthesis of insulin, as well as its secretion. Additionally, no such fructose potentiation of tolbutamide—induced insulin secretion was observed. This latter fact indicates that fructose does not possess all of the insulinogenic activity attributed to the glucose molecule. (Endocrinology91: 1493, 1972)