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Induction of endogenous antioxidants is one of the key molecular mechanisms of cell resistance to hypoxia/ischemia. The effect of severe hypoxia on the expression of cytosolic antioxidant thioredoxin-1 (Trx) in hippocampus and neocortex was studied in preconditioned and non-preconditioned rats. The preconditioning consisted of three trials of mild hypobaric hypoxia (360 Torr, 2 h) spaced at 24 h. Twenty-four hours after the last trial rats were subjected to severe hypobaric hypoxia (180 Torr, 3 h). Trx expression was studied by immunocytochemistry. In hippocampus severe hypobaric hypoxia rapidly induced Trx expression, which remained elevated still at 24 h. In neocortex the enhanced expression appeared only at 24 h. The preconditioning significantly augmented severe hypoxia-induced Trx-immunoreactivity at 3 h but not at 24 h. These findings point out that Trx contributes to mechanisms of brain tolerance to hypobaric hypoxia, especially in early periods after the exposure.