An important issue for in vivo gene therapy for cystic fibrosis (CF) is the percentage of cells within the CF airway that will require correction. In this study, we mixed populations of a CF airway cell line expressing either the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA (corrected cells) or a reporter gene in defined percentages. As few as 6–10% corrected cells within an epithelial sheet generated Cl⁻ transport properties similar to sheets comprised of 100% corrected cells. Cell–cell coupling may serve as the mechanism for amplification of the functional effects of corrected cells. These data suggest that in vivo correction of all CF airway cells may not be mandatory.