Adherence to host cells is a crucial step by which bacteria initiate an infection but the bacterial determinants of the process are, as yet, poorly understood. In an effort to identify bacterial adhesins responsible for Pseudomonas aeruginosa binding to host cells, we identified porin F (OprF) from the outer membrane of P. aeruginosa as adhesin for human alveolar epithelial (A549) cells. Bacterial adhesion assays with (35)S-labeled wild type P. aeruginosa and its isogenic mutant strain lacking OprF showed that the mutant strain binds 43% less than the wild type to A549 cells (P<0.01). In addition, bacterial binding is significantly reduced (P<0.01) when either A549 cells were pretreated with purified OprF or if bacteria were pre-incubated with a monoclonal antibody to OprF. Finally, ligand binding experiments in which purified OprF protein was added to A549 monolayers showed saturable binding. These data indicate that OprF contributes to bacterial adherence to A549 epithelial cells and could facilitate Pseudomonas interactions with the epithelium, including colonization of the airway epithelium or the initiation of pulmonary infection.