The specific activity of sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) in homogenates of rat kidneys increases when the dietary intake of potassium is chronically increased. The effect is seen first and is most prominent in the outer medulla, but large loads of potassium elicit an increase in the cortex as well. Levels of Na-K-ATPase in brian, liver, and muscle, by contrast, are unaffected by potassium loading. Although the changes in enzyme activity in the kidney resemble those reportedly produced by aldosterone, they are not induced by experimental sodium deprivation, and they can be evoked by potassium loading in the absence of the adrenal glands. The results suggest that Na-K-ATPase of renal tubular cells, presumably in the distal tubules and collecting ducts, plays an important role in the phenomenon of potassium adaptation and in the process by which potassium is excreted into the urine.