The macrophage markers non-specific esterase, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme were compared with conventional microglial and macrophage stains in the human central nervous system. In a series of specimens from cases of head trauma, conventionally fixed and embedded, the modified Weil-Davenport stain was unequivocally best for demonstrating reactive microglia. alpha 1-antichymotrypsin, however, was the most effective for showing macrophages in a series of specimens from patients with other conditions, which included inflammatory, neoplastic, and non-inflammatory diseases. The non-specific esterase reaction was unsatisfactory in tissues fixed in neutral formalin but was successful in fresh frozen tissue. In a series of specimens from cases of multiple sclerosis, non-specific esterase showed demyelination clearly and stained neuronal cytoplasm. It also stained macrophages but was less satisfactory for lipid-bearing phagocytes in multiple sclerosis than oil red 0.