CYSTIC fibrosis (CF) is a lethal genetic disease resulting in a reduced CI⁻ permeability¹, increased mucous sulphation², increased Na⁺ absorption³ and defective acidification of lysosomal vesicles⁴. The CF gene encodes a protein (the cystic fibrosis trans-membrane conductance regulator, CFTR⁵) that can function as a low-conductance Cl⁻ channel with a linear current-voltage relationship whose regulation is defective in CF patients^6–8. Larger conductance, outwardly rectifying Cl⁻ channels are also defective in CF and fail to activate when exposed either to cyclic AMP-dependent protein kinase A or to protein kinase C^9–13. The role of the outwardly rectifying Cl⁻ channel in CF has been questioned¹⁴. We report here that expression of recombinant CF genes using adeno-associated virus vectors in CF bronchial epithelial cells corrects defective Cl⁻ secretion, that it induces the appearance of small, linear conductance Cl⁻ channels, and restores protein kinase A activation of outwardly rectifying Cl⁻ channels. These results re-establish an involvement of outwardly rectifying Cl⁻ channels in CF and suggest that CFTR regulates more than one conductance pathway in airway tissues.