The effects of change in pharyngeal airway pressure on electromyographic (EMG) activity of a pharyngeal dilating muscle (genioglossus) were investigated in 20 anesthetized rabbits. In vagotomized animals, upper airway loading maneuvers (nasal occlusion) increased the peak inspiratory activity of the genioglossus (GG) muscle on the first occluded breath. In contrast, “unloading” maneuvers (switching from nose to tracheostomy breathing) decreased GG activity. To further characterize the GG response, sustained pressure changes were produced within the isolated upper airway. Negative pressure increased GG activity; positive pressure decreased it. A poststimulus effect consisting of increased GG activity compared with control was seen following both negative- and positive-pressure stimuli. Cyclical pressure changes applied to the isolated upper airway increased the GG activity. These observations indicate the presence of reflex pathways that regulate GG muscle activity in response to upper airway pressure loads. This reflex system appears to play a role in regulating GG activity during tidal breathing and could be important in ensuring pharyngeal airway patency.