It has been postulated that sleep disruption may change ventilatory chemoresponsiveness to hypercapnia and hypoxia and thereby contribute to the development of respiratory failure in some patients with obstructive sleep apnea syndrome (OSAS) or with other respiratory disorders. Some studies have demonstrated a reduction in ventilatory chemoresponsiveness in normal subjects after one night of total sleep deprivation. However, sleep fragmentation rather than total sleep deprivation is usual in patients. In this study, therefore, we measured hypercapnic ventilatory responsiveness (HCVR) and spirometry in 13 healthy male subjects (18 to 30 yr of age) after two consecutive nights of severe sleep fragmentation (arousal to an auditory stimulus after each minute of sleep) and compared the results with those obtained in the same subjects after normal sleep. Sleep fragmentation and normal sleep were separated by a week, and the order of intervention was randomized from patient to patient. No significant differences were observed in the slope or position of the HCVR curve after sleep fragmentation or in forced expiratory volumes. Although it is possible that a more prolonged period of sleep fragmentation than that used in this study may have an effect on HCVR, the results suggest that sleep fragmentation is an unlikely cause of progressive respiratory failure in patients with OSAS or with other respiratory disorders.