Ventilation is not constant during steady-state prolonged hypoxia. This raises questions as to the role of the carotid body (CB) in sustained hypoxia. Studies in awake goats using an extracorporeal CB circuit to allow separation of systemic (QMS) and CB blood gases provided evidence that prolonged hypoxia isolated to the CB causes time-dependent increased CB sensitivity to hypoxia. These findings were confirmed in recordings of afferent CB discharge in anesthetized goats. Studies in cats have been compatible with those in goats. It is concluded that prolonged hypoxic stimulation of the CB increases its sensitivity to hypoxia and is at least partly responsible for increased ventilatory drive during prolonged hypoxia such as during altitude acclimatization.