During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isometric handgrip at 25%, 50%, and 75% maximum voluntary contraction (MVC) in 9 human subjects with paced breathing. Similar experiments were performed in 11 additional subjects before and after partial neuromuscular blockade (intravenous curare) to isolate the influence of central command while minimizing force output and thus muscle afferent feedback. Before curare, handgrip at 25% and 50% MVC had no effect on MSNA, whereas handgrip at 75% MVC synchronized the MSNA to the handgrip such that MSNA was 5.7 +/- 1.3 times higher (mean +/- SEM, P < .001) during the contraction periods than during the relaxation periods. After curare, this synchronization of MSNA persisted without attenuation, even though force output fell to < 25% of the initial MVC. From these observations, we conclude that central command causes synchronization of motor activity and muscle sympathetic activity during intense intermittent isometric exercise.