An important mechanism controlling genioglossus (GG) muscle activity is the reflex response to negative airway pressure. We hypothesize that this reflex response may be lost during sleep and believe that this loss may be important in the pathogenesis of airway collapse during sleep. Thus, we determined the effect of non-rapid eye movement (NREM) sleep on the GG electromyogram (EMG) response to brief (0.2 to 0.6 s) episodes of negative pressure generation (NPG) in the upper airway of six normal subjects. Up to 100 NPGs (mean 58 +/- 12) were recorded both awake and during stable NREM sleep. During wakefulness, the change in GG moving time average EMG from basal to peak levels (during NPG) was 17.1 +/- 2.5 au (a 154 +/- 22% increase above basal levels). This response was markedly reduced during NREM sleep (2.7 +/- 1.2 au; p < 0.01). The latency of the GG EMG response was 53.8 +/- 11.5 ms during wakefulness (n = 6), but much longer during sleep (132.7 +/- 24.5 ms; n = 3; p < 0.03). We conclude that in normal subjects (1) the GG muscle responds to negative airway pressure by reflex activation during wakefulness, and (2) this reflex activation is reduced or lost during NREM sleep. We speculate that loss of this mechanism during sleep may contribute to pharyngeal collapse in obstructive apnea patients.