Reactive oxygen species (ROS) play key roles in the cascade of brain injury after stroke, and strategies to increase the antioxidant defenses of neurons after stroke hold great promise. In this study we evaluate the neuroprotective potential of using a herpes simplex viral vector to over-express catalase in rats. Vector was microinfused into the striatum either prior to or after middle cerebral artery occlusion (MCAO). Catalase over-expression was protective (relative to control vector) when the vector was delivered 14-16 h prior to ischemia, but not when delivered after ischemia. Thus, the timing of catalase over-expression relative to ischemia is a critical variable determining its potential therapeutic value.