Aim: The objective of these studies was to examine the effects of long-term vasopressin treatment on acid-base transporters in the collecting duct of rat kidney. Methods: Brattleboro rats were placed in metabolic cages and treated with daily injections of 1-desamino-8- D-arginine vasopressin (dDAVP), a selective V<sub>2</sub>-receptor agonist, or its vehicle (control) for up to 8 days. Results: dDAVP treatment resulted in a significant reduction in serum bicarbonate concentration, and caused the upregulation of key ammoniagenesis enzymes, along with increased urinary NH<sub>4</sub><sup>+</sup> excretion. Northern hybridization and immunofluorescence labeling indicated a significant increase (+80%) in mRNA expression of the apical Cl<sup>–</sup>/HCO<sub>3</sub><sup>–</sup> exchanger pendrin (PDS), along with a sharp increase in its protein abundance in B-type intercalated cells in the cortical collecting duct in dDAVP-treated rats. In the inner medullary collecting duct, the abundance of basolateral Cl<sup>–</sup>/HCO<sub>3</sub><sup>–</sup> exchanger (AE1) and apical H<sup>+</sup>-ATPase was significantly reduced in dDAVP-treated rats. Kidney renin mRNA increased significantly and correlated with an increase in serum aldosterone levels in dDAVP-injected rats. Serum corticosterone levels were, however, reduced and correlated with increased mRNA levels of renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and decreased mRNA expression of 11β-hydroxylase in the adrenal gland of dDAVP-injected rats. Conclusion: Chronic administration of dDAVP to Brattleboro rats is associated with the upregulation of PDS and downregulation of H<sup>+</sup>-ATPase and AE1 in the collecting duct, along with increased ammoniagenesis. Stimulation of the renin-angiotensin-aldosterone system and/or decreased glucocorticoid levels likely plays a role in the transduction of these effects.