Rationale: Efficient removal of apoptotic cells is essential for the resolution of acute pulmonary inflammation. Alveolar macrophages ingest apoptotic cells less avidly than other professional phagocytes at rest but overcome this defect during acute inflammation. Surfactant protein-A (SP-A) and surfactant protein-D (SP-D) are potent modulators of macrophage function and may influence clearance of apoptotic cells through activation of the transmembrane receptor SIRP. Objective: To investigate whether binding of SP-A and SP-D to SIRP on alveolar macrophages suppresses apoptotic cell clearance. Methods: Phagocytosis of apoptotic cells was assessed using macrophages pre-treated with SP-A, SP-D or the collectin-like molecule, C1q. Binding of SP-A and SP-D to SIRP were confirmed in vitro using blocking antibodies and fibroblasts transfected with active and mutant SIRP. The effects of downstream molecules SHP-1 and RhoA on phagocytosis were studied using SHP-1 deficient mice, sodium stibogluconate, and a Rho kinase inhibitor. Lipopolysaccharide was given to chimeric mice to study the effects of SP-A and SP-D binding on inflammatory macrophages. Results: Pre-incubation of macrophages with SP-A or SP-D suppressed apoptotic cell clearance. Surfactant surpression of macrophage phagocytosis was reversed by blocking SIRP and inhibiting downstream molecules SHP-1 and RhoA. Macrophages from inflamed lungs ingested apoptotic cells more efficiently than resting alveolar macrophages. Recruited mononuclear phagocytes with low levels of SP-A and SP-D mediated this effect. Conclusion: SP-A and SP-D tonically inhibit alveolar macrophage phagocytosis by binding SIRP. During acute pulmonary inflammation, defects in apoptotic cell clearance are overcome by recruited mononuclear phagocytes.