Increased episodes and duration of apnea during sleep associated with arterial oxygen desaturation have been reported after administration of flurazepam. We postulated that an alteration in respiratory control during sleep might be the underlying mechanism of this observation. Accordingly, we measured isocapnic hypoxic and hyperoxic hypercapnic ventilatory and arousal responses during natural (NS) and during flurazepam-induced (FS) sleep. We found no significant difference in the ventilatory response to hypoxia during FS compared with that during NS in 8 normal subjects. Similarly, although the ventilatory response to hypercapnia was performed in only 4 of the 8 subjects during FS, no significant difference from that during NS was noted in these subjects. There was, however, a significant decrease in the number of hypercapnic response tests in which arousal occurred after flurazepam administration (85% in NS versus 54% in FS; p less than 0.005). Additionally, an increase was seen in the mean PACO2 level at which arousal occurred during FS (51 +/- 1.6, means +/- SEM) as compared with that during NS (49 +/- 0.9; p less than 0.07). A similar but not significant decrease was noted in the number of hypoxic response tests in which arousal occurred (28% during NS versus 17% during FS). We conclude that while ventilatory responses to hypoxia and hypercapnia are normal during sleep after flurazepam administration, a decrease in arousal response is seen after administration of this drug in normal subjects. This alteration in arousal response may be the pathogenic mechanism of the increased duration of apnea reported in association with flurazepam.