We investigated the strength of the association between oxidative stress, hypoxia inducible factor 1 (HIF-1 alpha) and acute hypoxic ventilatory response (AHVR) after hypoxic training in elite runners. Six elite runners were submitted to 18-day of "living high-training low" (LHTL) and six performed the same training in normoxia. AHVR was measured during an acute hypoxic test before and after training. Plasma levels of protein oxidation (AOPP), malondialdehydes and (HIF-1 alpha) mRNA in the leukocytes were measured before and after the acute hypoxic test. LHTL increased AHVR and amplified the responses of HIF-1 alpha mRNA and AOPP (Delta(AOPP)) to the acute hypoxic test. Furthermore, between PRE and POST, the changes in Delta(AOPP) were correlated with the changes in AHVR (r=0.69, P=0.01). The ventilatory acclimatization to hypoxia occurring in athletes after LHTL seems to be modulated by oxidative stress. Furthermore, LHTL induced a higher sensitivity of HIF-1 alpha mRNA to acute hypoxia in elite athletes.