A controversy in the field of cystic fibrosis (CF) research has arisen concerning the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the transport of ATP. Does the CFTR actually conduct ATP or does it regulate the conductance of ATP? Recent findings either support or reject the hypothesis that the CFTR can transport ATP. In addition, recent research from several laboratories has suggested that ATP mediates its effects after traversing the plasma membrane and reaching the extracellular surface. The current model suggests that the released ATP exerts its various influences via a purinergic receptor to regulate outwardly rectifying chloride channels and epithelial sodium channels.