Early and late adjustment to potassium loading in humans. We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. “K balance” (urinary K excretion ∼80% of intake) was achieved in the second 24 hour period of K loading. This was associated with elevated plasma K and aldosterone, slightly negative sodium (Na) balance and stimulated plasma renin activity. At 20 days of K loading Na loss had been compensated. Plasma renin activity and aldosterone had returned to baseline, although the latter kept increasing after each single K meal. Compared to the first K meal, the K meals at 72 hours and 20 days of K loading were followed by more kaliuresis, while the natriuretic effect had disappeared. Abrupt discontinuation of K loading was followed by negative K balance, lasting only 24 hour, and by Na retention, lasting 72 hours. In conclusion, switching to a high K diet in humans is immediately followed by increased renal K excretion, and by Na loss. K excretion increases over a few days, while Na loss is halted. This can be explained by the rise in plasma aldosterone, secondary to elevated plasma K and renin activity. After weeks, renal adaptation forms an additional factor promoting K excretion and preventing natriuresis. The latter appears specifically from the Na retention which occurs after discontinuation of K loading in the absence of persistent aldosterone stimulation.