Tissues from 12 metastatic tumors of the brain were studied immunohistochemically with an antiserum to a glia-specific protein, astroprotein (glial fibrillary acidic protein, GFAP). Emphasis was laid on demonstrating the tissue architecture of metastatic lesions incorporating brain-derived components (astrocytes and glial fibers). Of 12 samples, 11 manifested a number of irregular indentations at the tumor surface. These indentations, which contained astrocytic elements, extended into the tumor tissue in a tapering fashion. In seven cases, the deeper stromal portions of the tumor also contained astroprotein (GFAP)-positive elements. The presence of this glia-specific protein suggests that the stroma of the tumor tissue may in part be derived from preexisting brain tissue. This peculiar tissue architecture of the tumor supports the hypothesis that some of the blood vessels that are located in the stroma of the tumor tissue are also derived from the brain. These observations may be important in understanding the partial preservation of the blood-brain barrier in metastatic brain tumors and the mode of growth of the metastatic lesion, and in selecting the type of chemotherapy that will be most effective in controlling this central nervous system complication of systemic malignancies.