We measured brain tissue Po2 in the frontal and occipital cortices, mid-brain and basal ganglia in monkeys for up to 5 hours after 16 min global brain ischemia to gain some insight into those factors responsible for the selective vulnerability of the brain to ischemic anoxia. Brain tissue Po2 measurements were made with gold microelectrodes with tip diameters of 5 to 10 nm. Reoxygenation of the different brain regions occurred at different "apparent" cerebral perfusion pressures and times postischemia. Areas of low susceptibility to ischemic brain damage, such as the frontal cortex, were not consistently reoxygenated at lower perfusion pressures or earlier postischemia than were areas of high susceptibility such as the occipital cortex, basal ganglia and midbrain. These findings support earlier observations that perfusion defects and brain histologic changes are multifocal in nature after global brain ischemia. We suggest that the selective vulnerability of the brain to ischemia is attributable to the development of regional edema and a local increase in tissue pressure during ischemia thereby decreasing cerebral perfusion pressure and leading to local perfusion defects after restoration of circulation. Also, that the selective vulnerability of the brain is attributable to variable degrees of neuronal-glial edema and regional shifts in brain water during ischemia leading to the development of local perfusion defects and the expansion of lesions from areas of high to low vulnerability.