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Cystic fibrosis (CF) affects the function of multiple organs. The inability to maintain luminal hydration of ducts leads to their plugging and destruction of the affected organs. An exacerbating problem is the acidic pH of the fluid produced by CF patients’ secretory glands. This is best documented for pancreatic secretion. Alkaline fluid secretion requires vectorial transport of electrolytes and of HCO3 - . The mechanism of HCO3 - secretion by cystic fibrosis transmembrane conductance regulator (CFTR) expressing cells is not well understood. In the present communication we discuss results suggesting that CFTR itself can transport large amounts of HCO3 - and that HCO3 - transport by CFTR is mediated by a coupled, Cl- -dependent process that is different from a simple HCO3 - conductance.