Objective: Hemodynamic impairment in one hemisphere has been shown to trigger ipsilateral motor activation in the opposite hemisphere on functional imaging. We hypothesized that reversing the hypoperfusion would normalize the motor activation pattern. Methods: We studied four patients with high-grade stenosis and impaired vasomotor reactivity (VMR) but no stroke. Functional magnetic resonance imaging motor activation pattern before and after VMR normalization was compared with seven healthy control subjects scanned at an interval of 3 months using voxel-wise statistical parametric maps and region of interest analysis. Subjects performed a repetitive hand closure task in synchrony with 1 Hz metronome tone. We used repeated-measures analysis of variance to compute the interaction between group (patients/control subjects) and time by obtaining the average blood oxygen level dependent signal of three motor regions of interest in each hemisphere. Results: Two patients normalized their VMR after spontaneous resolution of dissection, and two after revascularization procedures. Both voxel-wise statistical maps and region of interest analysis showed that VMR normalization was associated in each case with a reduction in the atypical activation in the hemisphere opposite to the previously hypoperfused hemisphere (p > 0.001). Interpretation: In the presence of a physiological stressor such as hypoperfusion, the brain is capable of dynamic functional reorganization to the opposite hemisphere that is reversible when normal blood flow is restored. These findings are important to our understanding of the clinical consequences of hemodynamic failure and the role of the ipsilateral hemisphere in maintaining normal neurological function. © 2009 American Neurological Association.