To test the hypothesis that cerebral vasomotor reactivity (CVMR) is significantly more reduced in patients with hemispheric low-flow infarctions than in brain infarctions due to arterio-arterial embolism, a series of 64 consecutive patients with internal carotid artery occlusions were studied. CVMR was calculated from relative changes of blood flow velocity within the middle cerebral artery (MCA) measured by transcranial Doppler ultrasonography (TCD) during hypo- and hypercapnia. The configuration of the circle of Willis (COW) was also determined by TCD using common carotid artery compression tests. Anterior, posterior or ophthalmic artery collateral flow, and absence or combinations of these, were differentiated. CT scans were categorized as showing either no infarction (group I; n = 20) or territorial (group II; n = 28), or low-flow infarctions (group III; n = 16). As compared to normal, CVMR was significantly reduced but equal in groups I and II, however, even more reduced in group III. CVMR was lowest, and low-flow infarctions were most frequent in patients whose collateral hemispheric blood supply was from the ophthalmic artery as opposed to patients with a complete or nearly complete COW. Our findings indicate that low-flow infarctions in extracranial ICA occlusions represent brain damage due to a critical reduction in cerebral perfusion pressure, as opposed to thromboembolically induced lesions. The configuration of the COW seems to play the key role. Our findings also support the view that the pattern of hemispheric infarction seen on CT indicates the pathogenesis of stroke.