Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms. and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstraction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the caroid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death. (Pediatr Res 28: 374–378, 1990)