The role of respiratory mechanoreceptor stimuli in the arousal response to hypoxia was studied in three trained dogs. The dogs breathed through a cuffed endotracheal tube inserted through a chronic tracheostomy, and resistive loads of 8 to 49 cm H2O/L/s were added to the expiratory circuit. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and isocapnic progressive hypoxia was induced by a rebreathing technique. Arousal from sleep was determined by electroencephalographic and behavioral criteria. SaO2 at arousal from non-rapid eye movement (NREM) sleep increased progressively from 67.5 +/- 4.6% (mean +/- SEM), with no added resistance to 85.2 +/- 0.5% with the highest resistance (p less than 0.01), and from 60.6 +/- 0.6 to 81.6 +/- 0.4% during REM sleep (p less than 0.01). The added resistances also increased the steady-state (normoxic) level of alveolar PCO2 (PACO2). However, when PACO2 was increased to comparable levels by the addition of dead space rather than expiratory resistance to the breathing circuit, SaO2 at arousal from hypoxia was significantly lower than during expiratory resistive loading (p less than 0.05). We therefore conclude that mechanoreceptor stimuli arising from the ventilatory apparatus may contribute substantially to the arousal response to hypoxia.