Upper airway dilator muscles are phasically activated during respiration. We assessed the interaction between central respiratory drive and local (mechanoreceptive) influences upon genioglossal (GG) activity throughout inspiration. GGEMG and airway mechanics were measured in 16 awake subjects during baseline spontaneous breathing, increased central respiratory drive (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic negative pressure ventilation), both prior to and following dense upper airway topical anesthesia. Negative epiglottic pressure (Pepi) was significantly correlated with GGEMG across inspiration (i.e. within breaths). Both passive ventilation and IRL led to significant decreases in the sensitivity of the relationship between GGEMG and Pepi (slope GGEMG vs Pepi), but yielded no change in the relationship (correlation) between GGEMG and Pepi. During negative pressure ventilation, pharyngeal resistance increased modestly, but significantly. Anesthesia in all conditions led to decrements in phasic GGEMG, increases in pharyngeal resistance, and decrease in the relationship between Pepi and GGEMG. We conclude that both central output to the GG and local reflex mediated activation are important in maintaining upper airway patency.