Despite clinically available methods of diaphragm pacing, most patients with ventilator-dependent tetraplegia are still dependent on mechanical ventilation. Given the significant disadvantages of these devices, additional pacing options are needed. The objective of this study was to evaluate a novel and potentially more physiologic method of inspiratory muscle activation, which involves the application of high frequency (>200 Hz) stimulation to the ventral surface of the spinal cord in the high thoracic region. Studies were performed in 13 anesthetized dogs. High frequency spinal cord stimulation (HF-SCS) results in the activation of both the diaphragm and inspiratory intercostal muscles, in concert, at physiologic firing frequencies and the generation of large inspired volumes. Mean maximum firing frequencies of motor units in the parasternal (2^nd interspace), the external intercostal (3^rd interspace) and the diaphragm muscles were 10.6 ± 0.4, 11.7 ± 0.4 and 10.4 ± 0.3 Hz, respectively. These values were not significantly different than those occurring during spontaneous breathing at comparable inspired volumes. Maximum inspired volume was 0.93 ± 0.01 liters, which approximates the inspiratory capacity of these animals. Moreover, ventilation can be maintained on a chronic basis by this method (6 hours) without evidence of system fatigue. Our results suggest that HF-SCS results in activation of spinal cord tracts which synapse with the inspiratory motoneuron pools, allowing processing of the stimulus and consequent physiologic activation of the inspiratory muscles. HF-SCS has the potential to provide an effective method of inspiratory muscle pacing.