The effect of ethanol on the arousal response to airway occlusion during non-rapid eye movement sleep was studied in normal male subjects by testing the response to the occlusion of a face mask covering the nose and mouth on a control (C) and an ethanol (E) ingestion (2 ml/kg of 50% vodka) night in random order. In part A, five subjects breathed room air while in part B another five subjects breathed a mixture of air and oxygen adjusted to maintain a baseline sleeping SaO2 of 98%. In both parts, the time to arousal (TTA) was significantly longer on E nights. The TTA (mean +/- SEM) in part A on C versus E nights was 14.6 +/- 1.9 versus 20.6 +/- 1.4 s in stage 2 and 19.9 +/- 1.9 versus 29.2 +/- 1.8 in stage 3/4 (p less than 0.01). The corresponding values in part B were 22.2 +/- 3.6 versus 39.9 +/- 8.4 in stage 2 and 32.1 +/- 4.1 versus 63.7 +/- 9.6 in stage 3/4 (p less than 0.01). In part B, the maximum deflections in airway pressure were measured at a supraglottic location during airway occlusion to reflect the degree of inspiratory effort. The maximum airway suction pressure preceding arousal was significantly higher on E nights. Conversely, the rate of increase in inspiratory effort (maximum pressure) during occlusion was decreased by E. We conclude that moderate ethanol ingestion prolongs the time to arousal following airway occlusion by increasing the threshold of inspiratory effort associated with arousal and by decreasing the rate of increase in the magnitude of inspiratory efforts.