The purpose of this study was to assess the effect of triazolam (0.25 mg) on the arousal response to airway occlusion during nonrapid eye movement sleep in normal subjects. Six male subjects (mean age +/- SD, 28.1 +/- 7.1 yr) had their arousal response tested by occluding a mask covering the nose with the mouth sealed. After an adaptation night, subjects were studied on two consecutive nights. They ingested triazolam (0.25 mg) or placebo one-half hour before bedtime in a randomized double-blind crossover manner. Mask occlusion was performed 1 to 4 h after triazolam/placebo ingestion while the subjects breathed a mixture of air and oxygen adjusted to produce an arterial oxygen saturation of 98%. The maximal deflections in airway pressure were measured at a supraglottic location during airway occlusion to reflect the degree of inspiratory effort. The time to arousal (mean +/- SEM) was significantly longer on triazolam nights (32.0 +/- 5.2 versus 22.6 +/- 3.2 s, p < 0.01). The maximal airway suction pressure preceding arousal was higher on triazolam nights (26.5 +/- 2.0 cm H2O versus 20.0 +/- 1.2 cm H2O, p < 0.02). Conversely, the rate of increase in inspiratory effort (maximal pressure) during occlusion was not decreased by triazolam. We conclude that triazolam prolongs the time to arousal following airway occlusion by increasing the arousal threshold.