After chronic dietary potassium loading, epithelia in distal portions of the nephron and large intestine adapt to increase the rate of potassium secretion. This response to increased excretory loads of potassium maintains overall external balance and protects against the potentially lethal effects of hyperkalemia. The cellular adaptation in epithelia involved in preserving potassium homeostasis during potassium loading is characterized by an increase in the number of potassium pumps, reflected by an increase in Na-K-ATPase activity, in the basolateral cell membrane due, at least in part, to an amplification in the area of this membrane, and by an increase in transepithelial potential difference in most, but not all, adapted epithelia. These changes suggest that potassium adaptation is due to a step-up in the rate of cell uptake of potassium. In addition to chronic dietary loading, other conditions such as chronic renal insufficiency, elevated levels of mineralocorticoids, and administration of glucocorticoids are also characterized by accelerated rates of potassium secretion in the distal nephron and colonic mucosa and stimulation of Na-K-ATPase in basolateral portions of the cell membrane. These cellular changes in epithelia with increased capacity for potassium secretion are discussed in the context of our present understanding of mechanisms that control potassium excretion in urine and feces.