A new monoclonal antibody, MOMA-2, is described, which recognizes monocytes and macrophages in the mouse. The antibody reacts with the majority of mononuclear phagocytes in various tissues as determined by immunohistochemistry. It differs from other macrophage markers that have been described by the strong reaction with macrophages in the lymphoid organs such as the tingible body macrophages and macrophages in T cell-dependent areas. The antibody recognizes predominantly a cytoplasmic component, although a membrane component can also be demonstrated. Isolated Langerhans' cells, interdigitating cells and dendritic cells, members of the mononuclear phagocyte system that are involved in antigen presenting, stain weakly with the antibody. Because of the intense staining the antibody is very useful for defining tissue macrophages by immunohistochemistry.