Locomotor activity of rats with sham or ibotenic acid lesions of the medial prefrontal cortex (MPFC) was assessed after animals were exposed to a 15-min swim or control stress. Swim-stress-induced locomotor activity was augmented in the MPFC-lesioned rats. These and other data suggest that lesions of the MPFC are followed by an exaggeration of the normal behavioral response to stress. Dysregulation of dopamine transmission in the basal ganglia may be involved.