Renal tubular function, with special emphasis on potassium excretion, was studied in three patients with medullary sponge kidney (MSK). Urinary acidification and concentration abilities were impaired, while glomerular filtration rates remained normal. After short-term intravenous (IV) potassium chloride loading, maximal excretion of potassium was lower in the patients with MSK than in the normal controls. The kaliuretic response to IV sodium sulfate and acetazolamide infusion was maintained. The capacity of the kidney to sustain potassium balance under conditions of either long-term potassium loading or depletion was preserved. We have concluded that the medullary and papillary segments of the human collecting duct, have an important role in the handling of short-term potassium loading. The integrity of these segments, however, is not essential for adaptation to prolonged potassium surfeit or dietary depletion.