Sleep-disordered breathing is extremely common, affecting more than 2% of adults in the developed world and perhaps as much as 20% of middle-aged men. The condition is associated with episodic hypoxia due to recurrent apnoea. Additionally, episodic hypoxia occurs commonly in normal individuals and may even be induced as a strategy in exercise training and in the treatment of clinical disorders. We have shown that chronic episodic hypoxia impairs respiratory muscle function and CNS control of upper airway patency [1]. In this study, we tested the hypothesis that disruption of an endogenous antioxidant defence system exacerbates the effects of episodic hypoxia on upper airway muscle contractile function. Thirty two adult male Wistar rats were placed in restrainers with their heads in hoods in which the ambient oxygen concentration could be modified by controlling the gas supply to the hoods as previously described [2]. Sixteen rats were exposed to alternating periods of hypoxia (FiO₂ = 6-8%) and normoxia, twice per minute, 8 hours a day for 1 week (episodic hypoxia). The remaining sixteen animals were exposed to an air/air cycle under identical experimental conditions (control). In both groups, half the animals received daily injections of buthionine sulfoxamine (BSO; 50mg/kg i.p.), an inhibitor of the rate-limiting enzyme in glutathione synthesis [3]. The other half received daily vehicle injections. At the end of the 1-week treatment period, the sternohyoid muscles (a representative pharyngeal dilator muscle) were removed under anaesthesia (sodium pentobarbitone, 60mg/kg i.p.). In vitro isometric contractile properties were determined using strips of sternohyoid muscle in physiological salt solution at 30°C [4]. Fatigue properties were determined by stimulation of the muscle strips at 40Hz (train duration of 300ms), every 2 s for 5 min. Episodic hypoxia was associated with a decrease in sternohyoid muscle endurance, an effect that was exacerbated by treatment with BSO (e.g. tension at 3 min into the fatigue trial was 27±3% vs. *19±2% vs. *14±1%; mean±SEM; % of initial tension, control (n=8) vs. episodic hypoxia (n=8) vs. episodic hypoxia+BSO (n=6), *P<0.05 ANOVA vs. control). The results suggest that episodic hypoxia-induced oxidative stress contributes to impaired upper airway muscle performance in our animal model. Our results may have particular relevance to respiratory disorders associated with episodic hypoxia such as the sleep apnoea/hypopnoea syndrome.