Chronic intermittent hypoxia (CIH) is a central feature of the debilitating disorder- obstructive sleep apnoea. CIH has been shown to impair upper airway respiratory muscle function¹ perhaps due to oxidative and/or nitrosative stress². Peroxynitrite is both an oxidising and nitrating agent formed in vivo from the reaction of superoxide oxide and nitric oxide. Peroxynitrite may play an important role in modulating skeletal muscle function. Studies have suggested that peroxynitrite is capable of producing diaphragmatic contractile dysfunction³. We tested the hypothesis that peroxynitrite inhibits sternohyoid muscle contractile force in vitro. Earlier observations have suggested that muscle contraction accelerates the effect of exogenous oxidants due to the additive effect of oxidants produced from endogenous sources⁴ and therefore we also examined whether increased muscle contraction would accelerate and amplify the effect of peroxynitrite. Adult male Wistar rats were anaesthetized with 5% isoflurane and killed by spinal transection. Longitudinal strips from the sternohyoid (upper airway dilator) muscle were mounted isometrically in water-jacketed tissue baths at 27°C and either bubbled with a hyperoxic (95% O₂/5% CO₂) or anoxic (95% N₂/5% CO₂) gas mixture. Strips were set to optimal length and force-frequency relationship was assessed by stimulating the muscle at a frequency of 10, 50 and 100 Hz at 0, 30, 60 and 90 minutes. In a separate series of experiments, the force-frequency relationship was assessed every 10 minutes for two hours. Studies were conducted under paired conditions i.e. control vs. peroxynitrite (500mM)-treated muscle strips. Peroxynitrite had no effect on muscle function under hyperoxic (7.6 ±1.1 vs. 6.5±1.8 N/cm², mean±SEM, control vs. peroxynitrite at 90 min, P>0.05, Student’s paired t test, n=9) or hypoxic conditions (6.6±0.9 vs. 6.8±0.8 N/cm², control vs. peroxynitrite at 90 min, P>0.05, n=9). Increased muscle activation i.e. tetanic contractions every 10 minutes did not unmask a peroxynitrite effect under hyperoxic (9.2±1.4 vs. 7.6± 1.5 N/cm², control vs. peroxynitrite at 120 min, P>0.05, n=6) or hypoxic conditions (1.5±0.3 vs. 1.4±0.2 N/cm², control vs. peroxynitrite at 120 min, P>0.05, n=6). Preliminary studies using ebselen, a peroxynitrite scavenger, showed no improvement in hypoxia-induced muscle dysfunction. This suggests that endogenous peroxynitrite is not a major contributor to hypoxia-induced muscle dysfunction. In conclusion, peroxynitrite had no effect on sternohyoid muscle contractile force under hyperoxic or hypoxic conditions. A peroxynitrite-induced effect was not uncovered with increased muscle activation. This study suggests that upper airway muscle dysfunction associated with chronic intermittent hypoxia, which is ameliorated by antioxidant treatment,² is independent of peroxynitrite production.