The discovery ofFru-2, 6-P2 The effect ofglucagon on liver PFK In 1979, four groups of investigators (Castano et al., 1979; Clarke et al., 1979; Kagimoto & Uyeda, 1979; Pilkis et al., 1979) reported that the kinetic properties of PFK, measured in extracts of hepatocytes, were modified after incubation of the cells in the presence of glucagon. The hormonal action was to decrease the affinity of the enzyme for Fru-6-P and to increase the inhibitionby ATP. These effects were reported by the first and the third groups of investigators to be stable upon gel ifitration and purification of the enzymic prepara-tion. They were believed to be the consequence of a phosphorylation of PFK by cyclic AMP-dependent protein kinase (Castano et al., 1979; Kagimoto& Uyeda, 1979, 1980; Claus et al., 1980a). In contrast, when the same problem was re-investigated in this laboratory (Van Schaftingen et al., Abbreviations used: Fru-1, 6-P2, fructose 1, 6-bisphos-phate; Fru-2, 6-P2, fructose 2, 6-bisphosphate; Fru-6-P, fructose 6-phosphate; Glc-1, 6-P2, glucose 1, 6-bisphosphate; FBPase or FBPase 1, fructose 1, 6-bisphosphat-ase; FBPase 2, fructose-2, 6-bisphosphatase; PFK or PFK 1, 6-phosphofructo-1-kinase; PFK 2, 6-phosphofructo-2-kinase.