The morphological changes in the vascular endothelium caused by the administration of tumor necrosis factor-alpha (TNF-alpha) were studied in an experimental model of rat brain tumors. Wistar rats bearing implanted C6 glioma received human natural-type TNF-alpha (1.7 x 10(5) U/m2) through the carotid artery and were sacrificed 3 or 24 hours later. The endothelial cells of the tumor blood vessels, demonstrated by the immunoreaction to factor VIII-related antigen, were enlarged after TNF-alpha administration. Morphometry demonstrated that the nuclei of these endothelial cells were also increased in size. The endothelial cells in the brain remote to the tumor were not affected. An in vitro binding study demonstrated that TNF-alpha binding sites were distributed in the vascular endothelial cells within the tumor but not in the brain remote to the tumor. The selective effect of TNF-alpha on the tumor blood vessels in experimental brain tumors may be related to the selective distribution of the TNF-alpha binding site.