The topographic organization of cortical neurons is traditionally examined using histological procedures. Functional magnetic resonance imaging (fMRI) offers the potential noninvasively to detect interregional connectivity of human brain. In the brain, there is spontaneous firing of neurons even in the resting state. Such spontaneous firing will increase local blood flow, cause MRI signal fluctuations, and affect remotely located neurons through the efferent output. By calculating covariance of each voxel referenced to the time course of a selected brain region, it is possible to detect the neurons connected to the selected region. Using this covariance method, neural connectivity to primary motor cortex was assessed during a resting state in six healthy right-handed volunteers. This interregional connectivity is similar to connectivity established by other anatomical, histochemical, and physiological techniques. This method may offer in vivo noninvasive measurements of neural projections.