In the presence of vanadate, the optimum pH of renal (Na^+, K^+)-ATPase in rats is reduced and lies in the range of intracellular pH. This explains the difference in optimum pH observed with ATP extracted from equine muscle. Removal of vanadate from such ATP (with noradrenaline) raises the optimum to the accepted range obtained with synthetic ATP. Changes in the sensitivity of the enzyme to potassium concentration contribute to the alterations in optimum pH. The optimum pH of Mg-ATPase is unaffected by vanadate. Since vanadate may be an intracellular regulator of (Na^+, K^+)-ATPase changes of optimum pH in relation to intracellular pH could well contribute to the regulation of sodium pump activity.