In the present study, using the microdialysis technique, we provided evidence of the existence of hydroxyl radicals ( OH) in the striatum of awake rats under physiological conditions. This OH generation was virtually abolished by theN -methyl-d-aspartate (NMDA) receptor antagonist dizocilpine. On the contrary, it was significantly enhanced by the d o t ; NO synthase inhibitorN G -nitro-l-arginine methyl ester (l-NAME). The effect of l-NAME was completely reversed by l-arginine. These results suggest that the basal OH production is largely the consequence of an NMDA receptor-mediated glutamatergic tone. Moreover, it is likely that endogenous NO exerts an antioxidant activity in brain by preventing the rise in OH levels.