Abstract: Downregulation of nitric oxide in the brain of mice during their hypoxic preconditioning. J Appl Physiol91: 1193-1198,2001. An animal model of hypoxic preconditioning was produced in mice by repeated exposure to autohypoxic condition. The animals' tolerance times to hypoxia were 1.7, 1.8,2.1 and 2.3 times longer in runs 2,3,4 and 5,respectively, than that in run 1, and their oxygen consumption and heart and respiration rates were progressively and significantly slowed down during the repetitive exposure to hypoxia. L-arginine concentrat ion, nitric oxide(N0)synt hase positive cells, N 0synthase activity, and NO content in the whole brain and the subregions telencephalon, diencephalons,and brain stem were significantly increased during the first exposure and were, instead of continuing toincrease, significantly decreased in run 4 after the second and third exposure. Tolerance times under thehypoxic condition were significantly shortened and prolonged when preadministration of L-arginine andits analog, respectively, was made. These results indicate that NO in the brain is downregulated undercondition of hypoxic preconditioning and negatively involved in increased tolerance to hypoxia.