The epithelial cell is equipped with autoregulatory mechanisms that coordinate the rates of apical Na+ entry and basolateral Na+ extrusion, so that intracellular Na+ activity is maintained relatively constant when the rate of active Na+ transport changes. The increase of basolateral Na+ extrusion via the ouabain-inhibitable Na+,K+- ATPase during Na+ transport stimulation appears to be a result of both an increase in the number of operative Na+,K+-ATPase units in the basolateral cell membrane and in the Na+ turnover per Na+,K+-ATPase unit. Further, it is possible that the number of epithelial cells, which are involved in active Na+ transport, changes when the rate of Na+ transport is altered. Not only apical Na+ entry and basolateral Na+ extrusion are coupled, the basolateral membrane K+ conductance also changes in parallel with the rate of basolateral Na+ extrusion ("pump-leak parallelism"). These regulatory mechanisms serve to prevent inordinate changes in intracellular ion composition, transmembrane electrical potential difference, and cell volume. The cellular events taking place during stimulation of active transport resemble the changes during osmotic cell swelling. Hence, it is possible that cell volume changes are responsible for the coordination of apical and basolateral membrane properties.