A contributing factor to the failure of trials of neuroprotectants in acute ischemic stroke may be the differing vulnerability to ischemia of white compared with gray matter. To address this issue, we determined to establish the existence of potentially viable tissue in white matter and its evolution to infarction or salvage in both gray and white matter compartments in patients with ischemic stroke. Twenty-seven patients (mean age, 73.4 years) at a median of 16.5 hours after symptom onset were studied using the hypoxic marker 18F-misonidazole with positron emission tomography (PET). Tissue was segmented using an magnetic resonance probabilistic map. Although there was a greater volume of initially "at-risk tissue" in gray matter (58.3 cm3, 29.9-93.0 cm3 than white matter (42.0 cm3, 15.8-74.0 cm3; p <0.001) at the time of PET imaging, a higher proportion of this was still potentially viable in white matter (41.4%, 4.6-74.5%) than in gray matter (23.6%, 3.2-61.1%; p <0.05). However, a similar proportion in each compartment spontaneously survived. These data provide evidence for the existence of potentially salvageable tissue in human white matter and is consistent with it having a similar or even greater resistance to ischemia than gray matter. For the latter possibility, alternative therapeutic strategies may be required for its salvage.