Although the acute physiologic responses to apnea in patients with obstructive sleep apnea (OSA) have been well documented, the changes in these responses over the course of the disease have not been investigated. The purpose of this study was to use a canine model of OSA to examine the long-term effects of sleep apnea on the acute responses to airway occlusion during sleep. Four dogs were studied during a control period before induction of OSA, during a period of OSA (83-133 d), and following cessation of OSA. At least 6 mo after completion of the OSA protocol, the dogs were re-studied on a sleep fragmentation protocol (30-60 d) to determine the impact of a similar degree of sleep disruption, without OSA, on the acute responses to airway occlusion. OSA and sleep fragmentation both resulted in lengthening of the time to arousal in response to acute airway occlusion (p < 0.02) and in greater arterial oxygen desaturation (p < 0.05), peak inspiratory pressures (p < 0.003), and surges in maximum systolic and diastolic blood pressure during airway occlusion (p < 0.01). There were no differences between the changes observed during OSA and during sleep fragmentation. We conclude that the changes in the acute responses to airway occlusion resulting from OSA are primarily the result of the associated sleep fragmentation.