More than half of differentiating spermatogenic cells undergo apoptosis before maturing into spermatozoa during mammalian spermatogenesis. These cells are selectively and rapidly eliminated through phagocytosis by Sertoli cells, a testicular somatic cell type possessing phagocytic activity. We have investigated the mechanism by which Sertoli cells specifically recognize and phagocytose apoptotic spermatogenic cells and the consequences of phagocytosis. We showed by in vitro as well as in vivo analyses that Sertoli cells recognize apoptotic spermatogenic cells through the binding of their surface receptor, class B scavenger receptor type I, to phosphatidylserine that is expressed on the surface of spermatogenic cells during apoptosis. The inhibition of phagocytosis in live animals resulted in a decrease in the number of epididymal sperm. These results suggest that phosphatidylserine-mediated phagocytosis of apoptotic spermatogenic cells by Sertoli cells is required for the efficient production of sperm.