Many theories have been proposed to explain the regulation of renal ammoniagenesis during chronic metabolic acidosis but none of these is entirely satisfactory. Since the activity of each of the enzymes in this pathway greatly exceeds the maximum rate of ammonium production in vivo, even when physiological substrate concentrations are used in this calculation, it follows that ammoniagenesis must be inhibited in the intact animal. We shall present a novel hypothesis for the regulation of the maximum rate of ammoniagenesis which emphasizes the fact that ATP is a product of this pathway and that a limited rate of ATP utilization could control its maximum velocity during chronic metabolic acidosis. To test the validity of our hypothesis, a quantitative analysis of the pathways of ATP production and utilization in the kidney will be reviewed. This approach is similar to one already proposed for the regulation of the maximum rate of ketogenesis in the liver.