We studied ventilation, arterial blood gas tensions, and the ventilatory and airway occlusion pressure responses to hypercapnia of eight cats during wakefulness, quiet (slow-wave) sleep, and active (rapid-eye-movement) sleep. Responses to hypercapnia were measured before and during added airway resistance. Ventilation decreased, and arterial PCO2 increased during both slow-wave and rapid-eye-movement sleep. Unloaded ventilatory and airway occlusion pressure responses to hypercapnia decreased during slow-wave and rapid-eye-movement sleep as well. Flow-resistive loading caused awake cats to increase their occlusion pressure response to hypercapnia, thereby preserving their ventilatory responses. In contrast, during both slow-wave and rapid-eye-movement sleep, cats showed no augmentation of the occlusion pressure response and concomitant decrease of the ventilatory response to hypercapnia with the load. Thus, sleep was associated with loss of flow-resistive load compensation. It is postulated that, in an appropriate setting, this phenomenon could serve a protective function by decreasing the chances for progression from partial to complete upper airway obstruction during sleep.