Dipalmitoyl phosphatidylcholine (DPPC) is a major phospholipid constituent in the pulmonary surfactant, whereas lysophosphatidylcholine (Lyso-PC) is a minor constituent, this membrane phospholipid being produced at inflammatory sites in association with activation of phospholipase A₂. To determine the role of these two different forms of phospholipids in the phagocytic function of alveolar macrophages (AM), we examined the effects of DPPC or Lyso-PC on Fc-mediated phagocytosis. We demonstrated a significant decrease of the ingestion activity of AM for anti-sheep erythrocyte immunoglobulin G-coated sheep erythrocytes (EA: IgG) by DPPC. On the other hand, Lyso-PC caused significantly increased ingestion of EA: IgG by AM. These data indicate that increase of Lyso-PC due to the hydrolysis of DPPC through activation of phospholipase A₂ may up-regulate AM-mediated phagocytic functions in the alveolar milieu associated with infections and inflammation. DPPC may suppress and stabilize the AM-mediated phagocytosis in the normal alveolar environment.