Pendrin (encoded by Pds, Slc26a4) is a Cl⁻/HCO₃⁻ exchanger expressed in the apical regions of type B and non-A, non-B intercalated cells of kidney and mediates renal Cl⁻ absorption, particularly when upregulated. Aldosterone increases blood pressure by increasing absorption of both Na⁺ and Cl⁻ through increased protein abundance and function of Na⁺ transporters, such as the epithelial Na⁺ channel (ENaC) and the Na⁺-Cl⁻ cotransporter (NCC), as well as Cl⁻ transporters, such as pendrin. Because aldosterone analogs do not increase blood pressure in Slc26a4^−/− mice, we asked whether Na⁺ excretion and Na⁺ transporter protein abundance are altered in kidneys from these mutant mice. Thus wild-type and Slc26a4-null mice were given a NaCl-replete, a NaCl-restricted, or NaCl-replete diet and aldosterone or aldosterone analogs. Abundance of the major renal Na⁺ transporters was examined with immunoblots and immunohistochemistry. Slc26a4-null mice showed an impaired ability to conserve Na⁺ during dietary NaCl restriction. Under treatment conditions in which circulating aldosterone is increased, α-, β-, and 85-kDa γ-ENaC subunit protein abundances were reduced 15–35%, whereas abundance of the 70-kDa fragment of γ-ENaC was reduced ∼70% in Slc26a4-null relative to wild-type mice. Moreover, ENaC-dependent changes in transepithelial voltage were much lower in cortical collecting ducts from Slc26a4-null than from wild-type mice. Thus, in kidney, ENaC protein abundance and function are modulated by pendrin or through a pendrin-dependent downstream event. The reduced ENaC protein abundance and function observed in Slc26a4-null mice contribute to their lower blood pressure and reduced ability to conserve Na⁺ during NaCl restriction.