The recent proposal that Dra/Slc26a3 mediates electrogenic 2Cl⁻/1HCO₃⁻ exchange suggests a required revision of classical concepts of electroneutral Cl⁻ transport across epithelia such as the intestine. We investigated 1) the effect of endogenous Dra Cl⁻/HCO₃⁻ activity on apical membrane potential (V_a) of the cecal surface epithelium using wild-type (WT) and knockout (KO) mice; and 2) the electrical properties of Cl⁻/(OH⁻)HCO₃⁻ exchange by mouse and human orthologs of Dra expressed in Xenopus oocytes. Ex vivo ³⁶Cl⁻ fluxes and microfluorometry revealed that cecal Cl⁻/HCO₃⁻ exchange was abolished in the Dra KO without concordant changes in short-circuit current. In microelectrode studies, baseline V_a of Dra KO surface epithelium was slightly hyperpolarized relative to WT but depolarized to the same extent as WT during luminal Cl⁻ substitution. Subsequent studies indicated that Cl⁻-dependent V_a depolarization requires the anion channel Cftr. Oocyte studies demonstrated that Dra-mediated exchange of intracellular Cl⁻ for extracellular HCO₃⁻ is accompanied by slow hyperpolarization and a modest outward current, but that the steady-state current-voltage relationship is unaffected by Cl⁻ removal or pharmacological blockade. Further, Dra-dependent ³⁶Cl⁻ efflux was voltage-insensitive in oocytes coexpressing the cation channels ENaC or ROMK. We conclude that 1) endogenous Dra and recombinant human/mouse Dra orthologs do not exhibit electrogenic 2Cl⁻/1HCO₃⁻ exchange; and 2) acute induction of Dra Cl⁻/HCO₃⁻ exchange is associated with secondary membrane potential changes representing homeostatic responses. Thus, participation of Dra in coupled NaCl absorption and in uncoupled HCO₃⁻ secretion remains compatible with electroneutrality of these processes, and with the utility of electroneutral transport models for predicting epithelial responses in health and disease.