Adenovirus vectors are efficient vehicles for in vivo gene transfer to many different cell types. Recombinant adenovirus vectors containing exogenous genes for transfer are derived from adenovirus type 5 and are made replication deficient by the deletion of the E1 region. Based on the observation that many natural adenovirus infections are targeted to airway epithelial cells, a replication-deficient adenovirus vector was constructed containing the cystic fibrosis transmembrane conductance regulator cDNA for the potential therapy of the respiratory manifestations of cystic fibrosis. Using this vector, the normal human CFTR cDNA has been successfully transferred to airway epithelial cells of experimental animals via the trachea. This finding has led to the development of human gene therapy protocols for the evaluation of the safety and efficacy of adenovirus-mediated CFTR cDNA transfer to lungs of individuals with cystic fibrosis. In addition to the airways, adenovirus vectors have been demonstrated to mediate in vivo gene delivery to cells of the liver, blood vessels, brain, muscle, heart, peritoneum, and salivary glands. Adenovirus vectors containing marker genes have also been demonstrated to transfer genes to human tumor cells in nude mice. Such vectors may be useful for a variety of therapeutic applications for in vivo gene transfer for the therapy of cancer and other diseases.