A new functional magnetic resonance imaging (fMRI) technique is proposed based on nulling the extravascular gray matter (GM) signal, using a spatially nonselective inversion pulse. The remaining MR signal provides cerebral blood volume (CBV) information from brain activation. A theoretical framework is provided to characterize the sources of GM-nulled (GMN) fMRI signal, effects of partial voluming of cerebrospinal fluid (CSF) and white matter, and behaviors of GMN fMRI signal during brain activation. Visual stimulation paradigm was used to explore the GMN fMRI signal behavior in the human brain at 3T. It is shown that the GMN fMRI signal increases by 7.2%+/-1.5%, which is two to three times more than that obtained with vascular space occupancy (VASO)-dependent fMRI (-3.2%+/-0.2%) or blood oxygenation level-dependent (BOLD) fMRI (2.9%+/-0.7%), using a TR of 3,000 ms and a resolution of 2 x 2 x 5 mm(3). Under these conditions the fMRI signal-to-noise ratio (SNR(fMRI)) for BOLD, GMN, and VASO images was 4.97+/-0.76, 4.56+/-0.86, and 2.43+/-1.06, respectively. Our study shows that both signal intensity and activation volume in GMN fMRI depend on spatial resolution because of partial voluming from CSF. It is shown that GMN fMRI is a convenient tool to assess CBV changes associated with brain activation.