Abnormalities of cerebral blood flow during and following hypoxia and ischemia contribute to the progression of tissue injury. Oxidative stress during and following hypoxia is known to markedly increase superoxide anion concentration. There is conflicting evidence that the concentration of superoxide anion regulates cerebral blood flow through its effect on vascular tone, although difficulties in measurement of superoxide anion complicate these studies. In order to test the hypothesis that changes in cerebral blood flow during and following hypoxia are due to changes in extracellular superoxide anion levels, we examined tissue oxygen levels by fiberoptic oximetry and superoxide anion levels using a previously validated cytochrome c coated electrode on the cortical surface and correlated these measurements to cerebral blood flow measured by laser Doppler in rats subjected to 20 min of hypoxia followed by hyperoxic reoxygenation recovery. The results showed a burst of superoxide anion with the onset of reoxygenation that temporally correlated with a transient peak in tissue oxygen tension lasting 10 min. and was eliminated by pretreatment with Cu-Zn superoxide dismutase conjugated to polyethylene glycol. Cerebral blood flow did not differ during hypoxia or recovery in the polyethylene glycol conjugated superoxide dismutase and control treatment groups. This study demonstrated no effect of increased superoxide anion concentration on cerebral blood flow during hyperoxic recovery following hypoxia.