During receptor-mediated phagocytosis, macrophages release toxic molecules such as hydrogen peroxide which enable them¹ to kill antibody-coated tumour cells² and parasites³, too large to consume. Previous workers observed that while peroxide was clearly responsible for cytolysis of certain antibody-coated tumour cells^2,4,5, extracellular catalase was unable to inhibit this cytolysis, and they suggested that macrophages secrete peroxide into a protected cleft between the phagocyte and target. We have tested this and report here that the space beneath macrophages spread on glass surfaces is accessible to proteins with a molecular weight (MW) as large as 200,000 but the space beneath macrophages plated on glass surfaces coated with phagocytosis-promoting ligands is impermeable to proteins as small as 50,000 MW. It appears indeed that macrophages form a protein-tight seal at the periphery of their contact with ligand-coated surfaces and thereby create a closed compartment between the cell and the target.