Sleep apnea syndromes and nonapneic arterial oxygen desaturation during sleep are reported more commonly in men than in women. Because men have recently been shown to have a considerably reduced hypoxic ventilatory response (HVR) during sleep, we questioned if this finding would apply to women as well. Accordingly, we measured isocapnic hypoxic responsiveness in 6 normal women during wakefulness and all stages of sleep during both follicular and luteal phases of the menstrual cycle. During non-REM sleep, women were found to maintain their waking levels of HVR, measured as the slope of the relationship between ventilation and decreasing hemoglobin saturation. Hypoxic ventilatory response fell to 70% of the awake value during REM sleep, which was a significant change (p less than 0.05). Although HVR tended to be greater in the luteal than in the follicular phase of the menstrual cycle, both awake and asleep, this was significant only in Stage 2 sleep (p less than 0.05). When compared with recently reported men studied in this laboratory, these women demonstrated significantly less awake HVR even when corrected for body surface area (p less than 0.05). During sleep men and women had similar hypoxic responses, although this represents a considerable decrement in the awake response in the men and little change in the women. How these findings relate to the observed sexual differences in "sleep disordered breathing" is speculative.