During rapid eye movement (REM) sleep, hypoxia and hypercapnia occur in conjunction with hypoventilation. Although the hypoxic ventilatory response has previously been shown to be reduced in REM sleep, the hypercapnic ventilatory response (HCVR) has not been studied during REM sleep in adult humans. We therefore measured the ventilatory response to hypercapnia in 12 sleeping adults using a modified rebreathing method. The HCVR was significantly reduced in all stages of sleep compared with that during wakefulness (1.60 +/- 0.19 SEM L/min/mmHg CO2), falling to less than half the waking HCVR during non-REM sleep (0.75 +/- 0.08 L/min/mmHg CO2), with a further significant drop during REM sleep when HCVR was less than a third of that during wakefulness (0.45 +/- 0.10 L/min/mmHg CO2). The decreased ventilatory responses to hypercapnia and hypoxia in REM sleep help explain REM-related hypoxemic episodes.