Tissue levels and in vivo release of glutamate were measured in caudate-putamen of rat brain after a unilateral 6-hydroxydopamine lesion of meso-striatal/meso-cortico-limbic dopamine neurons. The results were compared with glutamate levels from corresponding regions in sham-injected animals. The unilateral dopamine lesion induced a bilateral increase of tissue levels of glutamate (45% ipsilateral and 39% contralateral to the lesion). Extracellular levels of glutamate as measured by microdialysis were also bilaterally increased (107% ipsilateral and 94% contralateral to the lesion). The results indicate that mesencephalic dopamine neurons regulate neuronal glutamate in ipsilateral as well as contralateral caudate-putamen.