The distribution of transferrin receptor (TfR) in normal human brain-tissue obtained at autopsy and in brain-tumor biopsy specimens from 27 patients was determined by immunohistochemistry using two specific murine monoclonal antibodies against human TfR. The tumors studied included 10 glioblastomas multiforme (GBM's), nine other glial tumors, and eight meningiomas. In normal brain, TfR was detected primarily in endothelial cells; rare glial cells also contained immunoreactive product. All tumors contained TfR-positive cells, although the intensity (number of cells stained) and pattern (focal vs. diffuse) of staining varied with the histopathological type of the tumor. Among gliomas, the most intense staining was seen in GBM's, especially in areas of pseudopalisading where virtually all cells were stained. A rough correlation between tumor grade, number of positively stained cells, and staining pattern was seen in the other astrocytic tumors. By contrast, all meningiomas demonstrated an identical and characteristic focal staining pattern. Considering the differential immunostaining for TfR between normal and neoplastic tissue, the authors conclude that TfR may be an appropriate target for monoclonal antibody-directed brain-tumor immunotherapy, especially in more malignant tumors such as GBM's.