Monoclonal antibodies that recognize either neurofilaments or glial filaments were used with the peroxidase-antiperoxidase (PAP) method to retrospectively study 100 tumors of the central and peripheral nervous systems in paraffin-embedded sections. Only neoplasms of putative neuronal origin or with presumed neuronal differentiation (paraganglioma, ganglioglioma, ganglioneuroblastoma, ganglioneuroma, neuroblastoma, ovarian teratoma and pheochromocytoma) contained tumor cells with immunoreactive neurofilament, but such cells were more common in the more differentiated or benign neoplasms in this category. Glial filament immunoreactivity was observed in tumor cells of glial origin and in tumor cells with foci of glial differentiation arising within the central nervous system, consistent with findings from previous studies using anti-glial-filament antisera. With the exception of a benign cystic teratoma, no glial filament immunoreactivity was observed outside the central nervous system. Some immunoreactive neurofilaments, but not glial filaments, were arranged in presumably abnormal balls, cords, or clumps within tumor cells, possibly reflecting cytoskeletal alterations related to neoplastic transformation. These findings indicate that monoclonal antibodies against intermediate filament proteins such as neurofilaments and glial filaments retain their specificity and sensitivity when employed in paraffin sections in conjunction with the peroxidase-antiperoxidase method. They suggest that such reagents are useful probes for the evaluation of the histogenesis or degree of differentiation in human nervous system tumors. Finally, they permit the speculation that the analysis of the intermediate filaments of tumor cells, as contrasted with those in normal cells, may provide new insights into the biology of neoplasms.