Nitric oxide has been implicated in mediating the neurotoxic effects of ischemia in the brain. However, studies of the effects of nitric oxide inhibition with nitric oxide synthase inhibitors have provided controversial results. One of the reasons for the controversy may be related to the specificity of the nitric oxide synthase inhibitors, such as Nw-nitro-L-arginine methylester (L-NAME), which has recently been questioned. The present work investigated the possible interaction of L-NAME with the enzyme catalase in vitro. Catalase is an iron containing enzyme which could potentially interact with the iron-binding groups of L-NAME. Since the normal function of catalase in the brain is to remove excess hydrogen peroxide, the inhibition of this process could have potentially toxic effects. L-NAME was found to attenuate the catalase inhibiting effects of the known catalase inhibitor cyanamide in vitro, suggesting a competition between cyanamide and L-NAME for catalase. In addition, L-NAME by itself attenuated catalase activity in vitro. These results indicate that in addition to inhibiting nitric oxide synthase, L-NAME may have effects on catalase activity.