Vacuolar H+ ATPases participate in renal hydrogen ion secretion in both the proximal and distal nephron. These plasma membrane forms of the vacuolar H+ ATPase are regulated physiologically to maintain the acid-base balance of the organism. Proton transporting renal cells have requirements for constitutive acidification of intracellular compartments for normal endocytic and secretory functions. Recent experiments have begun to reveal how the kidney regulates these proton pumps independently. Vacuolar H+ ATPases are a family of structurally similar enzyme which differ in the composition of specific subunits. Cytosolic regulatory enzymes are present in renal cells which may affect vacuolar H+ ATPases in certain membrane compartments selectively. The vacuolar H+ ATPase in the plasma membrane of intercalated cells resides in a specialized proton-transporting apparatus that translocates the enzyme between an intracellular membrane pool and the plasma membrane in response to physiologic stimuli.