Functional magnetic resonance imaging (fMRI) provides an indirect measure of cerebral activation that could be altered by factors directly affecting cerebral blood flow independent of changes in neuronal activation. Presently, we investigate how changes in blood pressure (BP) affect the activation detected with fMRI. fMRI scans were acquired in 33 rats under control conditions and following transient BP increases (norepinephrine, IV) or decreases (arfonad, IV) with and without electrical stimulation of the forepaw. Voxels correlating to either the stimulation or the change in BP time courses were identified. During transient hypertension, irrespective of forepaw stimulation, BP increases (i.e., >10 mm Hg) produced a transient increase in the blood oxygen level-dependent (BOLD) intensity resulting in a significant numbers of voxels correlating to the BP time courses (P < 0.05), and the number of these voxels increased as BP increased, becoming substantial at BP > 30 mm Hg. The activation patterns with BP increases and stimulation overlapped spatially resulting in an enhanced cerebral activation to simultaneous forepaw stimulation (P < 0.05). BP decreases (>10 mm Hg) produced corresponding decreases in BOLD intensity, causing significant numbers of voxels correlating to the BP decreases (P < 0.005), and these numbers increased as BP decreased (P < 0.001). The BP decreases and stimulation time courses and responses were distinct, and hypotension did not affect the detection of the activation response to forepaw stimulation. The results indicate that substantial hypertension accompanying a stimulation paradigm produces a BOLD response that enhances the cerebral activation detected, whereas hypotension does not affect the detection of neuronal activation but does produce responses that could be interpreted as a 'deactivation'.