Using magnetic resonance (MR) echo-planar imaging (EPI), we recently demonstrated the presence of low-frequency fluctuations (< 0.1 Hz) in MR signal intensity from the resting human brain that have a high degree of temporal correlation (p < 10(-3)) within and across associated regions of the sensorimotor cortex. These fluctuations in MR signal intensity are believed to arise from fluctuations in capillary blood flow and oxygenation. A substantial overlap between the activation map generated by bilateral finger tapping and temporally-correlated voxels from the sensorimotor cortex obtained during rest was observed. In the work reported here, we investigated whether respiratory hypercapnia, which is known to suspend spontaneous oscillations in regional cerebral blood flow, influences these low-frequency fluctuations. The magnitude of low-frequency fluctuations was reversibly diminished during hypercapnia, resulting in a substantial decrease of the temporal correlation both within and across contralateral hemispheres of the sensorimotor cortex. After the breathing mixture was returned to ambient air, the magnitude and spatial extent of the temporal correlation of low-frequency fluctuations returned to normal. Results of this study support the hypothesis that low-frequency physiological fluctuations observed by MR in the human cortex and spontaneous flow oscillations observed in early studies by laser-Doppler flowmetry (LDF) in the cortex of the rat are identical and are secondary to fluctuations in neuronal activity.