Severe head injury often causes an increase in intracranial pressure (ICP) and decreases in cerebral blood flow (CBF) and cerebral oxygen delivery (CO2del). To determine if this reduction in CBF and CO2del would produce cerebral ischemia and if this reduction would be abrogated by maintaining global cerebral perfusion pressure (CPP), we studied CPP, ICP, CBF, CO2del, cerebral oxygen extraction ratio (CO2ER), and cortical water content (CWC) in a porcine model of focal cryogenic brain injury. Fifteen mature swine were randomized to two groups. The experimental group (n = 7) had a brain lesion and was studied for 24 hours. The control group (n = 8) was instrumented only. Cryogenic injury significantly increased ICP and decreased CBF and CO2del compared with controls. There were no significant differences in CPP between the groups for the entire experiment, and the CPP was well above the ischemic threshold. The CO2ER significantly increased in the first three hours after brain injury. However, CO2ER in experimental animals tended to decrease 12 hours after brain injury and was not significantly different from that in controls. Cryogenic injury significantly increased the CWC in the lesioned hemisphere. These data indicate that focal brain injury results in persistent ischemia despite the normalization of CPP, suggesting that a significant increase in cerebral vascular resistance (CVR) occurs after brain injury. We conclude that in addition to maintenance of CPP, intervention to reduce CVR may be important in the management of brain injury.