The overall objective of the proposed research is to elucidate the mechanisms of those components of the ventilatory response to hypoxia which may be altered by disease states. Of primary interest will be the non-chemoreceptor (central nervous system-mediated) depression of ventilation by hypoxia. The threshold of this phenomenon will be determined in unanesthetized chemodenervated goats. The potential clinical significance of the phenomenon will be studied in experiments involving decreases in oxygen delivery to the brain of unanesthetized goats by a variety of clinically relevant means (e.g. anemia, carboxyhemoglobinemia, decreased brain blood flow). In these studies the energy metabolism of the brain (oxygen and glucose consumption, lactate production) will be monitored to determine whether the nonchemoreceptor-mediated depression of ventilation by hypoxia is a manifestation of metabolic impairment. Further studies are contemplated to localize the probable site of action of brian hypoxia as a ventilatory depressant. In these studies on anesthetized cats the vulnerability of various regions of the brain to hypoxia, assessed in terms of regional augmentation of blood flow and regional changes in tissue oxygen tension, will be correlated with the ventilatory depressant effect. Finally control of breathing will be studied in two models of little studied, clinically encountered, disruptions of central nervous system physiology. The postictal state and hyperosmolar brain swelling.