Potassium depletion (K⁺-D) induces hypertrophy and hyperplasia of collecting duct cells, and potassium repletion (K⁺-R) induces regression of these changes. The purpose of this study was to examine the time courses of the changes in cellular composition, the origin of intercalated cells (ICs) and the mechanism responsible for these changes. SD rats received K⁺-depleted diets for 1, 7, or 14 days. After K⁺-D for 14 days some of the rats received normal diets for 1, 3, 5, or 7 days. In the inner stripe of the outer medulla, K⁺-D increased significantly the number and proportion of H⁺-ATPase-positive ICs, but decreased the proportion of H⁺-ATPase-negative principal cells (PCs). However, proliferation was limited to H⁺-ATPase-negative PCs. During K⁺-R, the cellular composition was recovered to control level. Apoptosis increased during K⁺-R and exclusively limited in H⁺-ATPase-negative PCs. Double immunolabeling with antibodies to PC and IC markers identified both cells negative or positive for all markers during both K⁺-D and K⁺-R. Electron microscopic observation showed that ultrastructure of AE1-positive some cells were similar to AE1-negative some cells during K⁺-R. LC3 protein expression increased significantly and autophagic vacuoles appeared particularly in PCs on days 14 of K⁺-D and in ICs on days 3 of K⁺-R. These results suggest that PCs and ICs may interconvert in response to changes in dietary K+ availability and that autophagic pathways may be involved in the interconversion.