[eng] Surfactant protein A (SP-A) plays a critical role in the clearance of Pseudomonas aeruginosa from the lung. However, there is limited information about the interaction of this protein with P. aeruginosa cystic fibrosis (CF) isolates. We characterized the interplay between SP-A and a collection of isogenic sequential isolates from CF patients. We identified outer membrane protein OprH as a novel ligand for SP-A on P. aeruginosa. CF late isolates bound significantly less SP-A than their respective early isolates. This difference could be associated with a reduction in the expression of OprH. Binding of SP-A to OprH promoted phagocityc killing, thus late CF isolates were at least two-fold more resistant to SP-A mediated killing by human macrophages than their respective early isolates. We postulate that reduction of OprH expression is a previously unrecognized adaptation of P. aeruginosa to CF lung that facilitates the escape of the microorganism from SP-A-mediated phagocytic killing.