The present review deals mainly with the functional aspects of the response of insulin-producing cells to D-fructose. Attention is drawn to the insulinotropic action of the ketohexose and its modulation by environmental factors, the process of stimulus-secretion coupling involved in fructose-induced insulin release, and the changes evoked by D-fructose in the handling of ⁴⁵Ca and ⁸⁶Rb by isolated pancreatic islets. The anomeric specificity of the effects of D-glucose upon the metabolic, cationic and functional response of pancreatic islets to D-fructose, the effects of the ketohexose upon protein biosynthesis in isolated pancreatic islets and its effects upon glucagon release are discussed. An alternative hypothesis concerning the possible role of sweet receptors in the stimulation of insulin release by D-fructose is also discussed.