Two monoclonal antibodies to cells of monocyte/macrophage lineage were established using a human glial cell-rich fraction as the immunogen. The antibodies, named GP-1 and GP-2, were originally found to react with perivascular cells of the central nervous system. They are immunohistochemically applicable on routinely formalin-fixed, paraffin-embedded tissue sections. GP-1 binds to a lysosomal protein, and GP-2 to a carbohydrate epitope of the cell membrane and lysosomes. Among the visceral organs, GP-1 labeled blood monocytes, almost all kinds of tissue and infiltrating macrophages in both normal and diseased states, and renal tubules. GP-1 staining of tissue macrophages tends to be intensified under inflammatory conditions. GP-1 staining also suggested that perivascular cells and macrophages had different ontogeny. GP-2 immunostained monocytes, Kupffer's cells, red pulp macrophages, infiltrating macrophages and reactive microglia, but not alveolar or tingible body macrophages. Besides those macrophages, GP-2 stained mantle zone lymphocytes, some hematopoietic cells, pneumocytes and renal collecting ducts. The staining pattern of ligands on THP-1 and HL-60 neoplastic human macrophage cell lines was dissimilar to that of other macrophage markers, suggesting that they recognize unknown macrophage-related antigens.