Pendrin is a Na+-independent Cl-/HCO3- exchanger that mediates Cl- absorption and HCO3- secretion within the cortical collecting duct and connecting tubule of the kidney (1,2). In response to either aldosterone or angiotensin II administration pendrin abundance and function are upregulated, which enhances Cl- absorption, thereby contributing the hypertensive response observed following the administration of these hormones (3,4). With disruption of the gene encoding pendrin, Slc26a4, the hypertensive response to aldosterone administration is blunted (3). Moreover, following a NaCl-restricted diet, where circulating aldosterone and angiotensin II concentrations are appropriately increased, pendrin null mice excrete more Na+ and Cl- than wild type mice, which contributes to the lower blood pressure observed in the mutant relative to the wild type mice (5). The greater chloriuresis observed in the mutant mice most likely occurs from the absence of pendrin-mediated Cl- absorption. However, since pendrin does not transport Na+, the cause of the enhanced natriuresis observed in the pendrin null mice was not obvious and therefore was explored further. Thus, we examined the abundance of the major renal Na+ transporters (the Na/H exchanger, NHE3; the Na-K-2Cl cotransporter, NKCC2; the thiazide-sensitive NaCl cotransporter, NCC and the epithelial Na+ transporter, ENaC) in kidneys from wild type and pendrin null mice. Following a NaCl-replete diet, where circulating aldosterone and angiotensin II levels are appropriately suppressed, renal Na+ transporter abundance was similar in kidneys from pendrin null and wild type mice (5). However, following a NaCl-restricted diet, where circulating aldosterone and angiotensin II levels are increased or following the administration of aldosterone, ENaC abundance and function was lower in the pendrin null than in wild type mice (5). In particular, abundance of the β and the δ subunits of ENaC were reduced with inactivation mutations in Slc26a4. Moreover, the amiloride-sensitive component of transepithelial voltage was much lower in cortical collecting ducts from pendrin null relative to wild type mice (5). This pendrin-dependent change in ENaC abundance and function is not due to changes in circulating levels of hormones such as aldosterone, angiotensin II, thyroid hormone or glucocorticoids. Instead, it may be caused by changes in paracrine function or changes in distal delivery of HCO3-. Moreover, this effect of pendrin on ENaC abundance appears limited to kidney (5). In conclusion, pendrin contributes to the hypertensive response observed following the administration of aldosterone and angiotensin II by its regulated ability to absorb Cl- and through its ability to modulate ENaC-mediated Na+ absorption.