In many species the pancreatic duct epithelium secretes HCO₃⁻ ions at a concentration of around 140 mM by a mechanism that is only partially understood. We know that HCO₃⁻ uptake at the basolateral membrane is achieved by Na⁺-HCO₃⁻ cotransport and also by a H⁺-ATPase and Na⁺/H⁺ exchanger operating together with carbonic anhydrase. At the apical membrane, the secretion of moderate concentrations of HCO₃⁻ can be explained by the parallel activity of a Cl⁻/HCO₃⁻ exchanger and a Cl⁻ conductance, either the cystic fibrosis transmembrane conductance regulator (CFTR) or a Ca²⁺-activated Cl⁻ channel (CaCC). However, the sustained secretion of HCO₃⁻ into a HCO₃⁻-rich luminal fluid cannot be explained by conventional Cl⁻/HCO₃⁻ exchange. HCO₃⁻ efflux across the apical membrane is an electrogenic process that is facilitated by the depletion of intracellular Cl⁻, but it remains to be seen whether it is mediated predominantly by CFTR or by an electrogenic SLC26 anion exchanger.