During normal voluntary movements, re-afferent sensory input continuously converges on the spinal circuits that are activated by descending motor commands. This time-varying input must either be synergistically combined with the motor commands or be appropriately suppressed to minimize interference. The earliest suppression could be produced by presynaptic inhibition, which effectively reduces synaptic transmission at the initial synapse. Here we report evidence from awake, behaving monkeys that presynaptic inhibition decreases the ability of afferent impulses to affect postsynaptic neurons in a behaviorally dependent manner. Evidence indicates that cutaneous afferent input to spinal cord interneurons is inhibited presynaptically during active wrist movement, and this inhibition is effectively produced by descending commands. Our results further suggest that this presynaptic inhibition has appropriate functional consequences for movement generation and may underlie increases in perceptual thresholds during active movement.