(1,5). However, when the same conjugates were used to introduce exogenous genes into cotton rats via the intratracheal route, the transgene was transiently expressed at low levels ( 12).We have demonstrated that in primary cultures of human tracheal epithelial cells, targeting the polymeric immunoglobulin receptor (pIgR)' can be used for the specific delivery of reporter genes to cells that bear the receptor (2). This receptor undergoes efficient internalization and is specifically adapted for the nondegradative transfer of large molecules. In addition, the cellular distribution of pIgR expression in the surface epithelium and serous cells of the submucosal glands conforms to that of the cystic fibrosis transmembrane conductance regulator in human airways (13,14). In this report, we show that tar-1. Abbreviations used in this paper: IL2r, human interleukin 2 receptor; pIgR, polymeric immunoglobulin receptor; SC, secretory component; SPDP, N-Succinimidyl 3-(2-pyridyldithio) proprionate; X-gal, 5-Bromo4-chloro-3-indolyl-,8-galactopyranoside.Gene Transfer into Respiratory Epithelial Cells In Vivo 493 J. Clin. Invest.