50% of the hindlimb vasodilatation evoked by systemic hypoxia is mediated by adenosine and 90% is nitric oxide (NO)-dependent (Marshall, 2000). We previously showed that the increase in femoral vascular conductance (FVC) evoked by systemic hypoxia was reduced by oxypurinol, a xanthine oxidase (XO) inhibitor: XO generates superoxide anions (O₂^–) from hypoxanthine, a metabolite of adenosine. In addition, infusion of exogenous SOD, which dismutes O₂^– to H₂O₂, potentiated the hypoxia-evoked increase in FVC (Pyner et al. 2003). The aim of this study was to investigate whether H₂O₂ generated by endogenous SOD contributes to hindlimb vasodilatation evoked by systemic hypoxia, particularly the adenosine-mediated component. In male Wistar rats (n=10) anaesthetised with Alfaxan (3.3mg.hr^-1 I.V.) arterial blood pressure (ABP) and femoral blood flow (FBF) were monitored and FVC was calculated (FBF/ABP) before and during a 5 min period of systemic hypoxia (breathing 8% O₂) or adenosine infusion into the hindlimb (1mg.kg^-1.min^-1 I.A.) before and during infusion of the cell permeant SOD inhibitor sodium diethyldithiocarbamate trihydrate (DETC; 5mg.kg^-1.min^-1 I.A.) to inhibit endogenous SOD. Responses were compared with Student’s paired t-test, P<0.05 considered significant. Hypoxia evoked a significant decrease in PaO₂ (88.5±1.6 to 27.9±0.39mmHg; mean±SEM) and ABP, and a significant increase in FBF and FVC, indicating hindlimb vasodilatation. After DETC, the fall in ABP was significantly attenuated (44±3 vs 35±3mmHg), and the increase in FBF and FVC showed a tendency to be attenuated (0.27±0.05 vs 0.19 ±0.07ml.min^-1 and 0.008±0.001 vs 0.006±0.001CU respectively) suggesting a reduction in the hindlimb vasodilatation evoked by hypoxia after inhibition of endogenous SOD. Adenosine infusion also evoked a significant decrease in ABP and significantly increased FVC, indicating hindlimb vasodilatation. After DETC, the fall in ABP tended to be attenuated (41±3mmHg vs 33±3mmHg; P=0.08). Further, instead of increasing, FBF fell (+0.09±0.03 vs -0.10±0.05ml) and the increase in FVC was significantly attenuated, by ~50% (0.005±0.0004 vs 0.002±0.001CU), showing that SOD inhibition significantly reduced the hindlimb vasodilatation evoked by exogenous adenosine. These results extend our previous findings (Pyner et al. 2003) and indicate that during hypoxia, XO metabolises adenosine to generate O₂^–, which is then converted to H₂O₂ by endogenous SOD and contributes to the hindlimb vasodilatation.