The relation between white-matter lesions (WMLs), demonstrated with magnetic resonance imaging, and regional cerebral blood flow (CBF), measured with dynamic positron emission tomography and [18F] fluoromethane, was investigated in 20 patients with atherosclerotic disease of the internal carotid artery. There was no correlation between the extent of small patchy WMLs and hemispheric CBF, but hemispheric CBF was significantly reduced in 5 patients with multiple large or confluent lesions. Distinct focal cortical CBF reductions were observed when large WMLs (greater than 5 mm) were located directly beneath the cortex, whereas large WMLs in deeper white matter were associated with a more diffuse decrease of cortical perfusion. There was no evidence of preferential CBF reduction in vascular border zones with increasing severity of WMLs or stenosis of the internal carotid artery. The side of previous transient ischemic symptoms correlated significantly with hemispheric CBF asymmetries, but not with asymmetries of WMLs and internal carotid artery stenosis. It can be concluded from these results that the presence of small patchy WMLs shown by magnetic resonance imaging cannot be used as evidence of impaired cerebral perfusion, while large lesions indicate clinically relevant cerebrovascular disease affecting cortical blood flow.