R enal cortical tubules consist of polarized epithelial cells where Na/H antiport activity has been demonstrated on the apical and/or basolateral membrane. Apical Na/H antiport activity plays an important role in transcellular bicarbonate (HCO3-) reabsorption, whereas basolateral Na/H antiport activity could be involved in transcellular HCO3- secretion as well as cell volume and pH control. To determine whether this heterogeneity in both localization and function is due to the existence of more than one Na/H antiporter, we studied the tissue distribution of Na/H antiporter mRNA by use of reverse transcription (RT) and polymerase chain reaction (PCR) in isolated nephron segments from rat renal cortex. The primers used were directed against the rat renal cortical Na/H antiporter cDNA which is homologous to the human growth factor-activatable Na/H antiporter. RT/PCR of beta-actin mRNA were performed as positive controls. Na/H antiporter mRNA expression in the proximal tubule was not detectable in S1 and S2 segments from superficial and most midcortical nephrons, which exhibit exclusively luminal Na/H antiport activity. It was expressed in S1 and S2 segments from juxtamedullary nephrons which have also basolateral Na/H antiport activity. Beta-actin mRNA was expressed uniformly in all segments of the proximal tubule. Na/H antiporter mRNA was also expressed in cortical thick ascending limb and cortical collecting duct, segments with basolateral Na/H antiport activity as well as in the glomeruli. In conclusion, at least two different Na/H antiporters exist in the renal cortex, i.e., the proximal tubule. The close correlation between functional localization of basolateral Na/H antiport activity and mRNA expression suggests that the rat kidney Na/H antiporter DNA homologous to the human growth factor activatable Na/H antiporter encodes a basolateral exchanger. The observed expression in a minority of midcortical proximal tubules could reflect a certain heterogeneity in these nephron segments.