BACKGROUND AND PURPOSE: Comparative studies across populations using functional magnetic resonance imaging (fMRI) rely on a similar relationship between blood oxygen level-dependent (BOLD) signal and neural activity. However, in elderly and patients with cerebrovascular disease, impaired cerebrovascular dynamics and neurovascular coupling may explain differences in BOLD contrast across populations and brain regions. The purpose of the study was to determine whether poststroke patients have regional heterogeneities of cerebrovascular reactivity (CVR) and their potential influence on voxel-wise motor-related BOLD signal. METHODS: Using fMRI, 8 fully recovered patients from stroke in the frontal lobe without cortical lesion in the regions of interest located in the primary sensorimotor cortex (SMC), supplementary motor area (SMA), and cerebellum (CRB) were compared with 8 healthy subjects. Motor-related BOLD signal changes (%SC) were evaluated during simple unimanual and bimanual tasks, and CVR was evaluated during hyperventilation (HV). Analyses were performed using Lipsia software in SMC, SMA, and CRB. RESULTS: In controls, amplitudes of BOLD signal were symmetrical in all regions of interest during all motor tasks and HV. In patients, %SC was decreased in SMC and SMA of the lesioned hemisphere despite their apparent anatomical integrity for all tasks. Impaired CVR was a predictor of impaired motor-related BOLD response in the SMC during contralateral movements (beta=-1.87; R=-0.75; P=0.03). CONCLUSIONS: These preliminary findings suggest that CVR heterogeneities may account for task-related BOLD signal changes in patients after stroke.