Functional activation of somatosensory cortex was studied in α- chloralose anesthetized rats by functional magnetic resonance imaging (fMRI), using both perfusion-weighted and T2*-weighted (blood oxygenation level dependent, BOLD) imaging. The sensitivity of functional activation was altered by ventilating animals for 3 minutes with 6% CO2. Before hypercapnic conditioning, electrical stimulation of the left forepaw at e frequency of 3 Hz led to an increase of signal intensity (relative to the unstimulated baseline condition) in the right somatosensory cortex by 6 ± 2% (means ± SD) in T2*-weighted images and by 45% ± 45% in perfusion-weighted images. After hypercapnic conditioning the signal intensity increase in perfusion- weighted images doubled to 91% ± 62% (P = 0.034), whereas that of T2*- weighted images only marginally increased to 7 ± 4% (not significant). This different behavior in both imaging modalities is interpreted as evidence for an increased flow response in combination with a higher oxygen extraction. Thus, the fMRI data reflect hypercapnia-induced resetting of the functional- metabolic coupling of the tissue during activation.