The fundamental characteristics that allow vectorial transport across an epithelial cell are the differential sorting and insertion of transport proteins either in the apical or the basolateral plasma membrane, and the preferential association of endocytosis and exocytosis with one or the other pole of the cell. Asymmetrical cellular structure and function, being manifestations of terminal differentiation, might be expected to be predetermined and invariant. Here we show that the polarity of transepithelial H⁺ transport, endocytosis and exocytosis in kidney can be reversed by environmental stimuli. The HCO₃-secreting cell in the cortical collecting tubule is found to be an intercalated cell possessing a Cl−/HCO−₃ exchanger in the apical membrane and proton pumps in endocytic vesicles that fuse with the basolateral membrane; the H⁺-secreting cell in the medullary collecting tubule has these transport functions on the opposite membranes. Further, the HCO−₃-secreting cell can be induced to change its functional polarity to that of the H⁺-secreting cell by acid-loading the animal.