Previous reports indicate that male rats given right (but not left) frontal cortical suction lesions develop hyperactivity accompanied by cortical norepinephrine depletions. In this study, female rats given such lesions to either hemisphere developed bilateral cortical norepinephrine depletions but no hyperactivity. Right lesion male rats developed both catecholamine depletions and hyperactivity. Thus, the lateralized hyperactivity response to these cortical lesions is sex-dependent and may involve sex differences in subcortical neural pathways.