The aim of this study was to assess whether oxidative stress induces deleterious NOS activity in the central nervous system (CNS). For this purpose, the mitochondrial toxin malonate, which promotes free radical production, was infused into the left striatum of rats. Forty-eight hours after injection, an increase in Ca-independent NOS activity was observed in the injected striatum. This increase was blocked by alpha-phenyl-tert-butyl-nitrone, a free radical scavenger, and by aminoguanidine, an inhibitor of NOS 2. Both these drugs reduced the malonate-induced striatal necrotic volume. These results suggest that in the CNS oxidative stress can induce a Ca-independent NOS, probably of type 2, which contributes to the lesion.