Hypoglossal motoneurons (HMNs) innervate all tongue muscles and are vital for maintenance of upper airway patency during inspiration. The relative contributions of the various synaptic inputs to the spontaneous discharge of HMNs in vivo are incompletely understood, especially at the cellular level. The purpose of this study was to determine the role of endogenously activated GABAA and glycine receptors in the control of the inspiratory HMN (IHMN) activity in a decerebrate dog model. Multibarrel micropipettes were used to record extracellular unit activity of individual IHMNs during local antagonism of GABAA with bicuculline and picrotoxin or glycine receptors with strychnine. Only bicuculline had a significant effect on peak and average discharge frequency, and on the slope of the augmenting neuronal discharge pattern. These parameters were increased by 30 ± 7% (p<0.001), 30 ± 8% (p<0.001) and 25 ± 7% (p<0.001), respectively. The effects of picrotoxin and strychnine on the spontaneous neuronal discharge and its pattern were negligible. Our data suggest that bicuculline-sensitive GABAergic, but not picrotoxin-sensitive GABAergic or glycinergic inhibitory mechanisms actively attenuate the activity of IHMNs in vagotomized decerebrate dogs during hyperoxic hypercapnia. The pattern of GABAergic attenuation of IHMN discharge is characteristic of gain modulation similar to that in respiratory bulbospinal premotor neurons, but the degree of attenuation (~25%) is less than that seen in bulbospinal premotor neurons (~60%). The current studies only assess effects on active neuron discharge and do not resolve whether the lack of effect of picrotoxin and strychnine on IHMNs also extends to the inactive expiratory phase.