The localization of S-100 protein, a nervous system specific protein, was studied immunohistochemically in sections of normal human brain and various brain tumors. In human brain, the specific positive reaction for S-100 protein was observed in astrocytes, oligodendrocytes, ependymal cells and epithelial cells of the choroid plexus. In human brain tumors, a positive reaction was observed in all cases of astrocytoma, glioblastoma, oligodendroglioma, ependymoma, choroidplexus papilloma, neurinoma and teratoma examined. A positive reaction was also observed in some cases of meningioma and hemangioblastoma. In astrocytoma and glioblastoma, the positive reaction for S-100 proten was weak in intensity and heterogeneous throughout the section in accordance with the increased histopathological malignancy. All metastatic brain tumors were negative for S-100 protein. From this immunohistochemical evidence it is concluded that the immunohistochemical examination of S-100 protein in human brain tumors may become a useful method for the diagnosis of human brain tumors, especially in relation to the histogenesis and degree of malignancy.