Despite extensive investigations, the determinants of the insulinotropic action of D-fructose still remain elusive. The major aim of the present article concerns several aspects of D-fructose metabolism in pancreatic islets. Emphasis is first placed on the possible participation of distinct enzymes, low-Km hexokinase, high-Km glucokinase and fructokinase in the phosphorylation of D-fructose by pancreatic islet homogenates. The uptake of D-fructose by intact islets and the generation of sorbitol by islets exposed to D-fructose are then briefly discussed. A detailed review of the metabolic fate of D-fructose in the islets is then presented based on the measurements of such variables as the conversion of D-[3-³H]fructose and D-[5-³H]fructose to either ³HOH or tritiated acidic metabolites and the paired ratio between the oxidation of ¹⁴C-labelled D-fructose and generation of ³HOH from tritiated D-fructose. Other variables under consideration include the oxidation of D-[1-¹⁴C]fructose, D-[2-¹⁴C]fructose, D-[3,4-¹⁴C]fructose, D-[6-¹⁴C]fructose and D-[U-¹⁴C]fructose and their conversion to either ¹⁴C-labelled acidic metabolites or amino acids. Complementary information is also provided on the concentration-related effects of D-glucose on these variables and the effects of D-fructose on D-glucose metabolism. Attention is also paid on the interference of D-glyceraldehyde, on one hand, and D-mannoheptulose on the other hand, upon the metabolism of D-glucose and/or D-fructose. Finally, attention is drawn to the effects of D-fructose on O₂ uptake and either the total or cytosolic content of ATP and ADP in pancreatic islets.