We used functional magnetic resonance imaging to investigate whether hemispheral hemodynamic impairment can play an independent role in the functional reorganization of motor-related activity in the brain. Fourteen patients with large vessel occlusion but no infarct performed a simple motor task with the hand contralateral to the occluded vessel. Statistical parametric maps of regional activity were generated to compare the distribution of motor-related activity among patients with that of control subjects. Patients were classified into normal or abnormal cerebral hemodynamics on the basis of intracerebral vasomotor reactivity using transcranial Doppler and carbon dioxide inhalation. Controls and patients with normal vasomotor reactivity showed typical motor activity in contralateral motor areas. When the 9 patients with abnormal vasomotor reactivity were compared with the 14 control subjects in a single analysis, unique motor activation was identified in ipsilateral motor regions in the nonhypoperfused hemisphere. In a confirmatory analysis, blood oxygen level-dependent (BOLD) signal intensity was averaged in prespecified motor regions of interest. A significant group by hemisphere interaction was identified, driven by higher ipsilateral and lower contralateral hemisphere BOLD signal in patients with abnormal vasomotor reactivity compared with controls (F=12.40, P=0.002). The average ipsilateral motor region signal intensity was also significantly higher in the subgroup of patients with abnormal vasoreactivity and no TIA compared with controls (P=0.04). Our results suggest that hemodynamic impairment in one hemisphere, even in the absence of any focal lesion or any symptoms can be associated with a functional reorganization to the opposite hemisphere. © 2006 ISCBFM. All rights reserved.