Traditionally, the neural control of movement has been studied by recording cell activity in restrained animals performing repetitive, highly trained tasks within a restricted workspace. However, the degree to which results obtained under these conditions are valid during natural, unconstrained behavior remains unknown. Using an autonomous, implantable recording system, we examined the relationships between the firing of motor cortex cells and forearm muscle activity in primates under three behavioral conditions: performance of a conventional torque-tracking task, unrestrained behavior, and natural sleep. We found strong correlations over long periods of daytime activity, suggesting a consistent relationship between cortex and muscles across the repertoire of awake behavior. The range of correlation values was comparable during task performance, but many individual cells exhibited significant differences across conditions. During the night, phases of sleep were associated with a cyclical pattern of cell and muscle activity. Across the population, the strength of cell-muscle correlations was related to preferred direction for daytime but not nighttime activity. The relationship of cells to behavior remained consistent over periods of several weeks. These findings extend the interpretation of results obtained under constrained conditions and are relevant to the development of neural prostheses for restoring natural movements to patients with motor deficits.