Hypocapnia due to hyperventilation reduces cerebral blood flow and volume. To investigate the effects of hyperventilation on the regional signal response to visual activation using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI), six volunteers were investigated during visual stimulation under normocapnia and hypocapnia conditions. Hyperventilation significantly decreased in visual cortex the BOLD MRI response to visual stimulation (3.97+/-0.5% [mean ( SD) in normocapnia vs. 0.77+/-0.7% in hypocapnia, P < 0.01]. In three of six subjects, functional signal changes were reduced to noise level. The reduced stimulus response during hyperventilation is probably due to a decreased overshoot in the blood oxygenation response. These results indicate that BOLD-contrast functional MRI is highly sensitive to pCO2 changes.