The purpose of this study was to assess the effect of triazolam (0.25 mg) on apnea duration and the arousal response to airway occlusion during sleep in patients with severe obstructive sleep apnea (OSA). Twelve male subjects with a mean (+/- SD) age of 46.6 +/- 14.1 yr and body weight of 260.8 +/- 55.9 lb were studied on two nights separated by a nonstudy night. They ingested triazolam (0.25 mg) or placebo 0.5 h before bedtime in a randomized double-blind crossover manner. In non-rapid-eye-movement (NREM) sleep, the mean (+/- SEM) duration of apnea/hypopnea was slightly increased (26.8 +/- 1.7 versus 23.8 +/- 1.2 s, p < 0.02) and the mean nadir in arterial oxygen saturation lower (80.1 +/- 1.9 versus 84.2 +/- 1.4%, p < 0.001) on triazolam nights. In NREM sleep, the deflections in esophageal pressure prior to apnea termination were higher on triazolam nights (53.3 +/- 5.4 versus 44.5 +/- 4.8 cm H2O, p < 0.001). However, the rate of increase in inspiratory effort (esophageal pressure deflections) during obstructive events was not decreased by triazolam. We conclude that triazolam increases the arousal threshold to airway occlusion, but that this results in only modest prolongation of event duration and increased desaturation at a dose of 0.25 mg in a group of large sleep apnea patients.