Sleep apnea syndromes are more common in men than in women. The ventilatory response to arousal from sleep may be an important determinant of respiratory stability/instability and could contribute to this sex difference. We therefore compared changes in ventilation, end-tidal carbon dioxide (CO2), upper airway resistance, heart rate, and finger photoplethysmogram pulse wave amplitude after both spontaneous and tone-induced arousal from non-rapid eye movement sleep in 13 men and 13 women. At sleep onset, ventilation fell and both upper airway resistance and end-tidal CO2 rose, but these changes were not different between sexes. Spontaneous arousal (duration, 6.6 +/- 0.2 seconds) resulted in a biphasic ventilatory response consisting of brief hyperventilation (5 seconds) followed by prolonged hypoventilation (30-40 seconds) on resumption of sleep. The biphasic ventilatory response was greater in men than in women and did not appear to be explained by different wake-to-sleep increments in end-tidal CO2 or upper airway resistance between sexes. Peripheral vasoconstriction with arousal was also greater in men than in women. Ventilatory responses were more marked after tone-induced versus spontaneous arousals and when subjects slept supine compared with the left lateral position. These results suggest that male sex and supine position are associated with greater ventilatory instability after arousal from sleep.