White matter changes are one potential etiology of behavioral changes in cerebrovascular disease. Whole brain diffusion tensor imaging-fractional anisotropy (DTI-FA) as a measure of apparent white matter integrity is related to cognitive function in cerebrovascular disease. However, white matter changes are not uniform, nor are their effects. We examine the relationship between regional differences in DTI-FA and cognition and mood in an ischemic-stroke sample. Participants were 108 patients, 3-6 months post stroke. Working memory, basic attention, recall, language, visuo-spatial, psychomotor, and encoding skills, and mood were assessed via neuropsychological evaluation. DTI scans were performed on a 1.5 T GE magnetic resonance imaging (MRI) system. Fractional anisotropy (FA) was calculated for frontal, temporal, occipital, and parietal regions using automated masks. Frontal and parietal FAs were more strongly and consistently related to cognitive and mood scores than were FA values from whole brain or temporal or occipital regions. This research contributes to our understanding of the etiology of cognitive and mood deficits in cerebrovascular disease.