Substance P was visualized in the rat and the guinea pig basal ganglia, mesencephalon and spinal cord after surgical unilateral cortical ablation. An increased density in substance P-like immunoreactive patterns in the substantia nigra was observed ipsilaterally to the lesioned hemisphere. These results, together with previous observations in cases of Alzheimer's disease presenting with asymmetric cortical atrophy, suggest an influence of the corticostriatal pathway on substance P-like immunoreactivity in these subcortical structures. Finally, these experiments proved to be a reliable animal model for the study of the effects of neocortical lesions on the neuropeptidergic innervation of certain subcortical regions.