Epithelial cells from normal human nasal turbinate and cystic fibrosis (CF) nasal polyps were isolated and inoculated in denuded, heterologous tracheal grafts that were implanted in immunocompromised mice. After three weeks, 22% of grafts were repopulated by the cell inoculum and exhibited bioelectric manifestations of ion transport. Compared with normal cells, grafts repopulated with CF cells retained bioelectric responses that reflect reduced cellular permeability to chloride ions (Cl-): (1) greater inhibition of short circuit current (Isc) when exposed to amiloride, (2) reduced Cl- diffusion potential difference, and (3) failure of isoprenaline (isoproterenol) to increase Isc. These observations suggest that the Cl- permeability defect of CF respiratory epithelial cells is preserved in heterologous culture, and is intrinsic to cells rather than secondary to local or circulating mediators.