Structural changes were studied on the kidney of a potassium-depleted man and on rat kidneys during potassium depletion and repletion. Light and electron microscopy revealed rapid disappearance of intracytoplasmic granules in the renomeduUary cells after potassium repletion in our patient as well as in rats. In potassium-depleted rats a series of ultrastructural changes, which were similar to those observed in the human kidney were seen with potassium repletion. Most of the granules were reduced in size and number, with loss of internal structure, shrinkage and condensation of their contents, and were almost totally eliminated by 72 h of potassium repletion. In some endothelial and interstitial cells, the granules were seen to be in the process of being extruded through an area of gap in the plasma membrane. The results indicate that most of the intracytoplasmic granules in the renal medulla rapidly disappeared by intracytoplasmic digestion and the rest of them were probably eliminated by exocytosis during reversal of potassium depletion nephropathy in man and rats.