ELEVEN ATHYMIC NUDE rats had stereotactic intracerebral inoculation of cells from one of three established human glioma cell lines (A172, A1207, and A1235). The implants grew progressively in 9 of 11 instances, which led to spontaneous death of the host in 14 to 37 days. For comparison, two Sprague-Dawley normal albino rats were implanted with the rat C6 glioma cell line. One rat died at 14 days, and the other was killed at Day 16. The human glioma cells developed into partially (A172, A1235) or totally (A1207) circumscribed tumor masses. Invasion, when present, was manifested as infiltrating prongs of cells rather than as individual cell infiltration. The growth of the human glioma cells was accompanied by a small zone of surrounding edema and marked central necrosis. These features were not encountered in the C6 implants. Inflammatory changes were minimal to nonexistent in all cases. All tumor lines produced internal cerebral herniation and neuraxis spread with implants seeded throughout the ventricular system, often associated with ventricular dilation. In situ hybridization, by the use of isotopic and nonisotopic detection methods, was used to study the cellular expression of the acidic fibroblast growth factor and basic fibroblast growth factor genes in A172 glioma xenografts. The expression of these genes was not seen in normal rat brain, but the genes were selectively overexpressed by the glioma cell implants, with especially high signal in the tumor periphery. This system may represent a good model with which to study the molecular pathology of human glial neoplasia and may provide a means by which to examine the potential effects of various treatment modalities on fibroblast growth factor gene expression and glioma growth.