To investigate the possible role of glial fibrillary acidic protein (GFAP) in cerebral ischemia, we have monitored the intracranial pressure (ICP) and local cerebral blood flow (ICBF) following bilateral carotid artery occlusion (BCAO) in GFAP-null mice and their wild type littermates. GFAP-null mice (B6, 129-Gfaptm/Mes) were obtained from Jackson Laboratories. The ICP and ICBF was continuously monitored during 15 minutes BCAO and reperfusion. The variation of the circle of Willis was also investigated in both GFAP-null and wild type mice. The breakdown of blood brain barrier (BBB) was assessed by immunohistochemical staining against mouse immunogloblins (IgG). A significantly more profound and immediate decrease in ICBF after BCAO was observed in GFAP-null mice (p < 0.04, ANOVA). GFAP-null mice also showed a significant increase (% change) in ICP after repeffusion (p < 0.05, ANOVA). There were no gross differences in the circle of Willis between GFAP-null and wild type mice. No abnormal IgG immunoreactivity was observed in the forebrain of both animals. These results indicate a high susceptibility to cerebral ischemia in GFAP-null mice and suggest an important role for astrocytes and GFAP in the progress of ischemic brain damage and increased ICP after cerebral ischemia with reperfusion. © Springer-Verlag 2002.