BACKGROUND: Whether loss of wakefulness itself can influence pharyngeal dilator muscle activity and responsiveness is currently unknown. A study was therefore undertaken to assess the isolated impact of sleep on upper airway muscle activity after minimising respiratory/mechanical inputs. METHODS: Ten healthy subjects were studied. Genioglossus (GG), tensor palatini (TP) and diaphragm (DIA) electromyography (EMG), ventilation and sleep-wake status were recorded. Non-invasive positive pressure ventilation was applied. Expiratory pressure was adjusted to yield the lowest GGEMG, thereby minimising airway negative pressure (mechanoreceptor) effects. Inspiratory pressure, respiratory rate and inspiratory time were adjusted until the subjects ceased spontaneous ventilation, thereby minimising central respiratory input. Muscle activity during wakefulness, wake-sleep transitions, stable non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep were evaluated in the supine position. RESULTS: In transitions from wakefulness to sleep, significant decrements were observed in both mean GGEMG and TPEMG (1.6 (0.5)% to 1.3 (0.4)% of maximal GGEMG; 4.3 (2.3)% to 3.7 (2.1)% of maximal TPEMG). Compared with sleep onset, the activity of TP during stable NREM sleep and REM sleep was further decreased (3.7 (2.1)% vs 3.0 (2.0)% vs 3.0 (2.0)% of maximal EMG). However, GGEMG was only further reduced during REM sleep (1.3 (0.4)% vs 1.0 (0.3)% vs 1.1 (0.4)% of maximal EMG). CONCLUSION: This study suggests that wakefulness per se, independent of respiratory/mechanical stimuli, can influence pharyngeal dilator muscle activity.