We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O₂ in N₂ for 240 s), hypoxic hypoxia (10% and 15% O₂ in N₂ for 90 s and 120 s, respectively), and hyperoxic hypercapnia (5% CO₂ in O₂ for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole-body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O₂ consumption or CO₂ production before and after chemodenervation, were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however after chemodenervation animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.