The changes in the extracellular concentrations of rat striatal H2O2, dopamine (DA) and its metabolites during middle cerebral artery (MCA) occlusion and reperfusion were simultaneously examined by microdialysis, and the relationship between the ischemia-induced release of DA and the generation of H2O2 was estimated by assessing the effect of the lesion of the substantia nigra (SN). In the rats without SN lesions, a significant increase in the striatal H2O2 level was observed during the ischemia and reperfusion phases. In the rats with SN lesions, the ischemia-induced H2O2 production was not attenuated. These results suggest that DA is not an important source of H2O2 in cerebral ischemia and reperfusion.