In animals, high-intensity unilateral stimulation of the phrenic nerve results in short-latency inhibition of phrenic and intercostal nerve activity bilaterally. This study provides the first demonstration in human subjects of a short-latency inhibitory response in the contralateral scalene, parasternal intercostal and diaphragm muscles to single stimuli delivered at cervical level to the phrenic nerve. Electromyographic (EMG) responses were recorded with intramuscular and surface electrodes. An inhibitory response with an onset latency of approximately 35 ms followed by a long-latency excitatory response at approximately 100 ms were observed in the three inspiratory muscles. The inhibition was evident in single trials, averaged EMG, histograms of the discharge of single motor units, and even when the phrenic nerve stimulus intensity was relatively low. Thus, the inhibition may be mediated by large-diameter muscle afferents. The latency of this potent inhibitory response to contralateral phrenic nerve stimulation is too long to be mediated via a simple spinal circuit and may involve a brainstem projection.