We will examine the factors which mediate ventilatory acclimatization in man and the regulation of brain ionic composition in respiratory acid-base distributions, with particular emphasis on the state of chronic hypoxia. To this end we will: a) determine the relative contribution of systemic and local factors to CSF (HCO3) and (H ion) regulation and the effects of duration of hypocapnia on this regulation in the awake dog; b) examine the influence of known and unknown ventilatory stimuli in brain ECF as potential mediators of ventilatory acclimatization-using ventricular perfusion in awake rats and dogs; c) determine the factors which regulate brain tissue pH and the relationship of changes in pHi to ventilatory acclimatization to hypoxia in dogs; and d) investigate the contribution of changes in brain neuro-transmitter metabolism to ventilatory acclimatization.