The hindlimb vasodilatation evoked by acute systemic hypoxia is ~50% mediated by adenosine and 90% nitric oxide-dependent¹. In normoxic (N) rats we showed that during acute hypoxia, xanthine oxidase (XO) metabolises adenosine to generate O₂^–, which is converted to H₂O₂ by endogenous SOD and contributes to the hindlimb vasodilatation². Chronic hypoxia is likely to increase O₂^– release via XO and the mitochondria. Thus, we have now investigated in chronically hypoxic rats, housed in 12% O₂ for 1, 3 and 7 days (1, 3 & 7CH), the contribution of H₂O₂ generated by endogenous SOD in hindlimb. Male Wistar 1, 3 and 7CH (n=9, 10 & 10) rats were anaesthetised with Alfaxan (12 mg.kg^-1.hr^-1 i.v.) and routinely breathed 12% O₂. Arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded and FVC was computed on-line (FBF/ABP) before and during a 5 min period of breathing 8% O₂ (acute hypoxia) before and during infusion of the cell permeant SOD inhibitor sodium diethyldithiocarbamate trihydrate (DETC; 5 mg.kg^-1.min^-1 i.a.). Responses before & after DETC were compared with Student’s paired t-test, & between groups by factorial ANOVA with Scheffe’s post hoc test; *: P<0.05. In 1, 3 and 7CH rats baseline P_aO₂ was lower than in N rats (47±1*, 45±2*, 46±2* vs 88±2 mmHg; mean±SEM), while baseline FVC was increased (0.011±0.001*, 0.010±0.001*, 0.010±0.001* vs 0.006±0.001 ml.min^-1.mmHg^-1), indicating a tonic hindlimb vasodilatation in 1-7CH rats. Breathing 8% O₂ caused a further decrease in P_aO₂ (33±1*, 30±1*, 31±1*), and increase in FVC (to 0.017±0.002*, 0.016±0.002*, 0.017±0.002*) in 1, 3 & 7CH rats to the same levels seen in N rats (28±2 mmHg; 0.016±0.001 ml.min^-1.mmHg^-1). During DETC infusion, baseline FVC was significantly reduced in 3CH, but not in 1 & 7CH rats. Further, acute hypoxia still caused a significant increase in FVC in 1, 3 & 7CH rats, but changes were smaller than before DETC (0.008±0.002 vs 0.003±0.001*, 0.007±0.002 vs 0.003±0.001*, 0.008±0.002 vs 0.003±0.001*). In N rats, the change in FVC tended to be reduced (0.009±0.001 vs 0.007±0.001 ml.min^-1.mmHg^-1). Thus the conversion of O₂^– to H₂O₂ by endogenous SOD apparently contributes to tonic muscle vasodilatation in 3CH rats and plays a greater role in the muscle vasodilatation evoked by acute hypoxia in 1, 3 and 7CH than N rats. We propose that during early chronic hypoxia the generation of O₂^– via adenosine and XO or by mitochondria is increased, and/or SOD activity is increased so enhancing the vasodilator role of H₂O₂.