The effects of acute metabolic acidosis, induced by the administration of NH4CI, and also plasma from acutely acidotic rats on the kinetics of phosphate-dependent glutaminase (PDG) from several animal tissues have been studied. During acute metabolic acidosis only the enzyme activity from kidney cortex was altered. On the other hand, PDG activity from the kidney cortex, small intestine and brain significantly increased in the direct presence of plasma from acutely acidotic rats at subsaturating concentration of glutamine. No such effect was observed with liver tissue. This kinetic behaviour leads to a significant depression in the Km values for the three affected enzymes but no variation in the Vmax. These results go to support the idea that PDG from the kidney cortex, brain and small intestine are kinetically and immunologically identical and also confirm that during acute metabolic acidosis a factor is released into the plasma, probably produced and concentrated by the kidneys, which induces a conformational chanNe in the enzyme from the kidney, brain and intestine and brings about a significant decrease in the Km for glutamine but no change in the Vmax.