The effect of pH on the activities of various enzymes along the ammoniagenic pathway was tested on dog kidney cortex homogenates in an attempt to identify the metabolic steps that could be directly influenced by a low pH in this species. The activity of alphaketoglutarate dehydrogenase was markedly stimulated by acidification of the medium that decreased abruptly the km for alphaketoglutarate. By contrast, succinyl CoA synthetase and malate dehydrogenase remained relatively insensitive to pH changes. The apparent km of malic enzyme for malate was markedly decreased by an acid medium. Therefore these findings suggest that an acid pH regulates the ammoniagenic pathway at two critical sites: alphaketoglutarate dehydrogenase and malic enzyme. These stimulated enzymatic activities may account for the changes in renal cortical concentrations of metabolites observed during metabolic or respiratory acidosis.