Hess, Haeckel and Brand [l] found that fructose-l, 6diphosphate (FDP)* is an activator of yeast pyruvate kinase (EC 2.7. 1.40). A similar effect has been reported for liver pyruvate kinase [2, 3]. Glucose&phosphate, fructose&phosphate, and 6-phosphogluconate were effective only at concentrations far above those occurring in viva [2]. No activation was found with fructose-l-phosphate and F-6-P under the conditions used in the pyruvate kinase assay [3]. In the course of studies on the metabolism of fructose we have found that FIP is an activator of pyruvate kinase at concentrations which occur in rat liver during perfusion with 10 mM fructose.