Newborn animals exhibit a biphasic response to hypoxia, with ventilation increasing and then declining. Our purpose was to define if this response could be supported by the pontile and medullary respiratory centers. Spontaneously breathing and paralyzed and ventilated decerebrate or anesthetized, vagotomized rats were studied from birth to 13 days thereafter. Peak integrated phrenic activity, or tidal volume, and frequency initially increased and then declined after inspired oxygen was reduced from hyperoxic to hypoxic levels; most animals became apneic in hypoxia. Apnea occurred in a greater proportion of animals and more quickly with more severe hypoxia. Following sectioning of the carotid sinus nerves, ventilatory activity declined with a change from hyperoxia to normoxia. We conclude that the biphasic ventilatory response to hypoxia represents a balance between synaptically-induced augmentations and reductions of brainstem neuronal activities. The carotid chemoreceptors play a fundamental role in the augmentations, and reductions appear dependent upon actions of hypoxia upon brainstem mechanisms.