Ventilatory drives are presumed to be important in the maintenance of ventilation during sleep. Although the hypercapnic ventilatory response has been shown to decrease during sleep, the hypoxic ventilatory response (HVR) has not been well studied in humans. We therefore measured the ventilatory response to isocapnic hypoxia in 6 sleeping men. The HVR, measured as the slope of the relation between ventilation and decreasing hemoglobin saturation, was significantly lower in all sleep stages than in wakefulness (1.07 +/- 0.19 SEM L/min/%saturation). The HVR decreased to two thirds of this waking value in non-REM sleep (0.63 +/- 0.09 L/min/%saturation) with a further significant decrease in REM sleep when HVR was less than one third of the waking value (0.33 +/- 0.04 L/min/%saturation). The decreased HVR may help to explain the REM-sleep-related hypoxemia found in normal persons and patients with various cardiovascular diseases.