Work from this laboratory has shown that the caudal hypothalamus modulates the cardiorespiratory responses to hypoxia. The purpose of this review is to describe the modulation of respiratory output by the caudal hypothalamus during hypoxia and how neurons in this area respond to hypoxia. The diaphragmatic activity response to hypoxia was significantly attenuated following microinjection of either cobalt chloride or kynurenic acid into the caudal hypothalamus of rats. In addition, caudal hypothalamic neurons in anesthetized rats and cats responded to hypoxia with an increased firing frequency. This response was maintained in the absence of input from the vagus and carotid sinus nerves in the cat. When recorded extracellularly or by whole-cell patch clamp in vitro, these neurons responded to hypoxia with an increase in firing frequency, membrane potential and inward current. These results suggest that the caudal hypothalamus exerts excitatory influence on respiration during hypoxia, that may originate from the ability of these neurons to sense changes in oxygen levels.