To assess the relationship between central control of upper airway and respiratory muscle, simultaneously recorded diaphragmatic electromyogram (EMGdi) and genioglossal EMG (EMG ge) responses to CO2 rebreathing were compared in five supine volunteers. Both EMGs were quantitated in terms of inspiratory peak moving time-average activity. In all subjects both EMGdi and EMGge increased linearly with increasing alveolar CO2 pressure (r = 0.93 +/- 0.04 and 0.87 +/- 0.07, respectively), resulting in a significantly linear EMGge vs. EMGdi relationship (r = 0.91 +/- 0.04). CO2 response slopes of both EMGs were similar and linearly related (r = 0.96, P less than 0.001) such that subjects with low EMGdi response also had a low EMGge response and vice versa. Although the onset of EMGge activity preceded that of EMGdi, and the pattern of both EMGs were different, inspiration duration of both EMGs were similar. These data indicate that in humans both diaphragm and genioglossus muscle share similar control mechanisms and suggest that upper airway function is intimately related to the regulation of breathing.