We investigated the effect of chemoreceptor stimulation and inhibition on total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep in healthy subjects. Chemoreceptor stimulation was accomplished with brief isocapnic hypoxia (n = 8). Minute ventilation increased to 150% of room air control. RL at peak inspiratory flow decreased to 66% of room air control. Resistive pressure-inspiratory flow plots demonstrated lower resistive pressures for a given inspiratory flow. Chemoreceptor inhibition was accomplished by abruptly terminating brief hypocapnic hypoxia with 100% O2 (n = 7). Minute ventilation decreased to 63% of room air control. RL calculated at peak inspiratory or fixed flow did not change significantly, and pressure-flow plots at nadir ventilation showed no systematic change from room air control. We conclude that 1) hypoxic chemoreceptor stimulation is associated with decreased RL and enhancement of pressure-flow relationships, suggesting increased upper airway caliber; 2) upper airway patency is not compromised during periods of low ventilatory drive in normal subjects; and 3) upper airway dilating muscles and thoracic pump muscles are optionally coordinated with increased and decreased ventilatory drive.