In recent years much interesting information about the mechanism of the Na<sup>+</sup>-K<sup>+</sup> activated ATPase has been obtained from investigation of the K<sup>+</sup>-activated phosphatase activity which appears to be catalysed by the same enzyme. Also several studies have indicated that a K<sup>+</sup>-activated p-nitrophenylphosphatase activity is intimately related to the ATPase activity. And then the exact relation of p-nitrophenylphosphatase activity to Na<sup>+</sup>-K<sup>+</sup> ATPase activity is not known. The effects of some ions and drugs on the p-nitrophenylphosphatase activity of the rat brain were investigated and the results were summarized as follows. 1. The p-nitrophenylphosphatase was stimulated markedly by low concentrations of K<sup>+</sup>, while the activity was activated slightly in the presence of Na<sup>+</sup> and oligomycin. 2. Addition of both ATP and Na<sup>+</sup> caused a remarkable increase in the activity of the K<sup>+</sup>-dependent phosphatase at low concentrations of K<sup>+</sup>. 3. In the presence of Na<sup>+</sup> and low concentrations of K<sup>+</sup>, oligomycin activated the p-nitrophenylphosphatase. 4. O1igomycin inhibited the stimulation of the enzyme activity caused by Na<sup>+</sup>+ATP. 5. Ouabain inhibited the K<sup>+</sup>-dependent p-nitrophenylphosphatase activity more in the presence of ATP and Na<sup>+</sup> than in their absence. 6. Quinidine inhibited both Na<sup>+</sup>-K<sup>+</sup> ATPase and p-nitrophenylphosphatase. These inhibitory effects of the drug were partially antagonized by increasing K<sup>+</sup> concentrations. The sensitivity of the K<sup>+</sup>-dependent p-nitrophenylphosphatase to quinidine was greater than the that of Na<sup>+</sup>-K<sup>+</sup> ATPase.