Surfactant protein A (SP-A) is a glycolsylated apoprotein that may facilitate bacterial phagocytosis and contribute to early bacterial clearance in the lung. The effect ofSP-A on attachment (or ingestion) of Staphylococcus aureus and type 25 pneumococci to rabbit alveolar macrophages and human monocyte-derived macrophages was studied. SP-A bound to S. aureus and type 25 pneumococci in a calcium-dependent manner. Bacteria-associated SP-A significantly increased attachment of S. aureus, but not pneumococci, to macrophages. Increased association of SP-Acoated S. aureus with macrophages appeared to consist mainly of attachment without ingestion, as determined by bactericidal tests and release of tritiated bacterial digestion products from macrophages. Preincubation of macrophages with SP-A did not increase attachment or ingestion of S. aureus or type 25 pneumococci, with or without the addition of immune opsonins. SP-A acts as a ligand to facilitate attachment of S. aureus to macrophages but has no effect on S. pneumoniae.