Arousal from sleep is associated with transient cardiorespiratory activation. Traditionally, this response has been understood to be a consequence of state-dependent changes in the homeostatic control of ventilation. The hypothesis predicts that the magnitude of ventilatory and cardiac responses at an arousal will be a function of the intensity of concurrent respiratory stimuli (primarily PCO(2)). Alternatively, it has been proposed that increased cardiorespiratory activity is due to reflex activation. This hypothesis predicts that the magnitude of the cardiorespiratory response will be independent of respiratory stimuli. To compare these hypotheses we measured minute ventilation (V(i)), heart rate (HR) and blood pressure (BP) during wakefulness and stage 2 sleep, while manipulating P(et)CO(2). Further, we assessed the magnitude of the response of these variables to an arousal from sleep at the various levels of P(et)CO(2). The subjects were male aged 18-25 years. P(et)CO(2) was manipulated by clamping it at four levels during wakefulness [wake eucapnic, sleep eucapnic (Low), and sleep eucapnic +3 mmHg (Medium) and +6 mmHg (High)] and three levels during sleep (Low, Medium and High). The average number of determinations for each subject at each level was 14 during wakefulness and 25 during sleep. Arousals were required to meet American Sleep Disorders Association criteria and were without body movement. The results indicated that average increases in V(i), HR and BP at arousal from sleep did not significantly differ as a function of the level of P(et)CO(2) present at the time of the arousal (all P > 0.05). Further, the magnitude of the ventilatory response to an arousal was significantly less than the values predicted by the homeostatic hypothesis (P < 0.05). We conclude that, in normal subjects, the cardiorespiratory response to an arousal from sleep is not because of a homeostatic response, but of a reflex activation.