OBJECTIVE: The aim was to investigate the effects of acute exercise under hypoxic condition and the repetition of such exercise in a 'living low-training high' training on the antioxidant/prooxidant balance. DESIGN: Randomized, repeated measures design. SETTING: Faculté de Médecine, Clermont-Ferrand, France. SUBJECTS: Fourteen runners were randomly divided into two groups. A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. INTERVENTION: A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. The first hypoxic group (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude) and the second normoxic group (NG, n=6) in normoxia. In control period, the runners were submitted to two incremental cycling tests performed in normoxia and under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) normalized for triacyglycerols and cholesterol were measured before and after the two incremental tests and at rest before and after training. RESULTS: No significant changes of MDA and AOPP level were observed after normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44% rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol normalized for cholesterol and triacyglycerols increased only after hypoxic exercise (10-12%, P<0.01). After training, FRAP resting values (-21%, P<0.05) and alpha-tocopherol/triacyglycerols ratio (-24%, P<0.05) were diminished for HG, whereas NG values remained unchanged. CONCLUSIONS: Intense exercise and hypoxia exposure may have a cumulative effect on oxidative stress. As a consequence, the repetition of such exercise characterizing the 'living low-training high' model has weakened the antioxidant capacities of the athletes.