Recent evidence suggests that colonization of the upper respiratory tract by gramnegative bacilli is mediated by adherence to regional epithelial cells. Buccal epithelial cells were obtained for study from 12 seriously ill patients, all of whom were colonized with Pseudomonas aeruginosa. In comparison to cells from uncolonized controls, cells obtained from these patients attached significantly more P. aeruginosa organisms during incubation in vitro. Although the sialic acid content of colonized patients' cells was less then that of controls' cells, removal of sialic acid from normal cells with neuraminidase did not increase bacillary adherence. Trypsinization of normal cells increased bacillary adherence and significantly reduced the amount of fibronectin on the cell surface. Both trypsinized normal cells and cells recovered from seriously ill colonized patients attached large numbers of P. aeruginosa organisms in vitro and demonstrated decreased fibronectin on the cell surface by immunofluorescent staining. These findings suggest that the host alteration associated with increased susceptibility to adherence by P. aeruginosa is the loss of fibronectin from the cell surface.