Phenotypic analysis demonstrated the expression of high levels of Annexin-V (AV) on the outer membrane of monocytes (MO) which was down-regulated by stimulation with lipopolysaccharide (LPS) or IL-4 and GM-CSF. In contrast, IFNγ stimulation increased the expression of AV on MO. Functional phagocytosis assays revealed that MO phagocytose phosphatidylserine (PS) expressing apoptotic cells (AC) in an AV-dependent manner. Both, blocking AV/PS interaction using a monoclonal anti-AV antibody and recombinant AV significantly diminished the phagocytosis of syngeneic AC. Interestingly, phagocytosis of allogeneic AC was selectively increased by blocking AV on MO, whereas blocking of PS on allogeneic AC led to a decrease. Taken together, our data show for the first time a distinct function of surface expressed AV in PS recognition and a subsequent ‘silent phagocytosis' by MO. These findings improve the understanding of AC clearance and might be of interest for the development of new anti-inflammatory cellular therapies.