The involvement of the ventromedial thalamic nucleus (VM) in mediating the local cerebral metabolic effects induced by unilateral substantia nigra (SN) electrical stimulation was investigated in the awake rat. Local cerebral glucose utilization (LCGU) was measured during ipsilateral SN-stimulation in VM-intact rats as well as in animals bearing 8 or 30 days old electrolytic VM-lesions, using the 14C-deoxyglucose quantitative autoradiographic method. In VM-intact rats, SN-stimulation enhanced LCGU in several bilateral components of the sensory motor, reticular, and limbic systems despite the lack of direct anatomical connections. Almost all these metabolic activations were no longer apparent one week following VM-lesion. In contrast, one month after the VM-injury, the above activations reappeared even more dramatically than in VM-intact animals especially on the contralateral side. It is concluded that SN-stimulation activates several brain regions of both hemispheres beyond the traditional motor areas, the role of the VM in mediating these activations is crucial, and the plasticity of the adult CNS allows for recovery of metabolic responsiveness in a disturbed system.