Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.