Survival times of female mice submitted to 6 atmospheres O2 were measured. Adrenal demedullation protected mice against high oxygen pressure (HOP), but not as much as adrenalectomy. Epinephrine partially reversed the protective effect of adrenalectomy, whereas cortisone and adrenal cortex extract could completely abolish the beneficial action of adrenalectomy. These observed facts seem to demonstrate that both the adrenal cortex and medulla have a detrimental effect in HOP, but the cortex has a more important role. With autonomic drugs the following observations were made: (a) Sympathomimetic drugs. Tryptamine and oxytyramine had a protective action, whereas epinephrine and norepinephrine had a detrimental influence, (b) Symatholytic drugs. Dibenzyline by itself had a protective effect and counteracted the detrimental effects of epinephrine and norepinephrine. (c) Parasympathomimetic drugs. Doryl (choline chloride carba-mate) and Mecholyl Chloride (metacholine chloride) bestowed a significant protection, (d) Parasympatholytic drugs. Atropine by itself decreased the survival time of mice exposed to 6 atmospheres of oxygen and completely nullified the protective effect of Mecholyl Chloride.