The topographical distribution of putative glutamatergic projections from the frontal cortex to the striatum and substantia nigra has been examined by measuring the high-affinity uptake of [14C]glutamate in synaptosomal preparations from rat anterior or posterior striatum and substantia nigra after a series of focal kainic acid lesions of the medial prefrontal cortex. The recorded changes in glutamate uptake suggest that the corticonigral glutamatergic projection arises from the rostral medial prefrontal areas, more caudal cortical areas projecting in turn to the anterior and posterior striatum.