The identities of the apical Cl⁻/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl⁻/OH⁻, Cl⁻/HCO₃ ⁻, and Cl⁻/formate exchange modes. The conclusion is that pendrin is an apical Cl⁻/base exchanger in the kidney proximal tubule and CCD and mediates Cl⁻/OH⁻, Cl⁻/HCO₃ ⁻, and Cl⁻/formate exchange.