Pancreatic duct cells (PDCs) secrete an alkaline, HCO₃^–-rich fluid, and this process is markedly reduced in cystic fibrosis as a result of dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR), an apical membrane chloride channel. However, it is still unclear the exact role that CFTR plays in HCO₃^– transport by PDCs. The initial step of HCO₃^– secretion is the uptake of HCO₃^– into the duct cells from the extracellular space. HCO₃^– can enter the epithelium either by the forward transport of HCO₃^–, via a basolateral Na⁺/HCO₃^– co-transporter, or by the diffusion of CO₂ into the cells, subsequent hydration to H₂CO₃ by carbonic anhydrase, and backward transport of protons via Na⁺-H⁺ exchangers and/or H⁺ pumps. HCO₃^– secretion across the apical membrane is thought to occur via CFTR and the SLC26 anion exchangers, SLC26A3 (DRA) and SLC26A6 (PAT-1). However, the relative importance of each of these apical transporters in HCO₃^– secretion is a controversial issue (Argent et al. 2006; Steward et al. 2005). Thus it is still unclear whether CFTR’s main role in HCO₃^– secretion is to secrete HCO₃^– directly, to provide a source of luminal Cl^– to support apical Cl^–-HCO₃^– exchange or to activate the apical Cl^–-HCO₃^– exchangers. It remains possible that all three mechanisms are utilized by the cells, perhaps under different physiological situations. To gain further insight into this issue we have been investigating the effects of CFTR expression on H⁺ and HCO₃^– transporters involved in ductal HCO₃^– secretion. To do this we have developed a novel system for efficient gene transfer of CFTR to polarized monolayers of CFPAC-1 cells (originally derived from a cystic fibrosis patient), using a recombinant Sendai virus construct (Yonemitsu et al. 2000), which does not impair cell polarity. This has allowed us to examine H⁺ and HCO₃^– transport activities in polarized CFTR-deficient and CFTR-expressing CFPAC-1 cells.