Alterations in extracellular (pHo) and/or intracellular pH (pHi) have significant effects on the apical Na+ conductive transport in tight epithelia. They influence apical membrane Na+ conductance via a direct effect on amiloride-sensitive apical Na+ channel activity and indirectly through effects on the basolateral Na+/K(+)-ATPase. Changes in pH also modulate the hormonal regulation of apical Na+ conductive transport. The pH sensitive steps in hormone action include: (i) hormone-receptor binding, (ii) increase in intracellular cyclic 3',5'-adenosine monophosphate (cAMP), (iii) mobilization of intracellular free Ca2+ ([Ca2+]i), and (iv) incorporation of new channels into the apical membrane or recruitment of existing channels. Alternately, changes in pH induce secondary effects via alterations in [Ca2+]i. A reciprocal relationship between pHi and [Ca2+]i has been demonstrated in renal epithelial cells. Natriferic hormones induce a significant increase in pHi. There is a strong temporal relation between hormone-induced increase in pHi and overall increase in transepithelial Na+ transport. This suggests that changes in pHi act as an intermediate in the second messenger cascade initiated by the hormones. Several natriferic hormones activate Na(+)-H+ exchanger, H(+)-ATPase, H+/K(+)-ATPase, H+ conductive pathways in cell membranes or potential-induced changes in pHi. However, changes in pHi do not seem to be essential for the hormone effect on Na+ conductive transport. It is suggested that the role of pHi changes during hormone action is permissive rather than strictly obligatory.