The effect of unilateral lesion of the rat substantia nigra with 6-hydroxydopamine (6-OHDA) was investigated on the endogenous contents of neurotensin (NT) and its binding site densities in the striatum and substantia nigra. Tyrosine hydroxylase (T-OH) activity, gamma-aminobutyric acid (GABA) content, binding site densities of dihydrotetrabenazine (TBZOH), a marker of dopaminergic synaptic vesicles, and of iodosulpiride, a ligand for dopamine D2 receptors, were also determined. Fourteen days following nigral lesions, these markers were analyzed quantitative autoradiography for NT, TBZOH and iodosulpiride binding site densities. Unilateral nigral lesion with 6-OHDA provoked only ipsilateral modifications in dopamine markers. T-OH activity and TBZOH binding site densities significantly decreased in both the ipsilateral striatum and substantia nigra. Iodosulpiride binding sites decreased in the substantia nigra and increased in the striatum on the ipsilateral side. In contrast to these unilateral changes observed for dopamine markers, dramatic increased in NT contents were found in both the ipsi- and contralateral striata. No change was found in nigral NT levels on either side. On the other hand, NT binding sites decreased in the ipsilateral striatum and substantia nigra, which reflected the destruction of dopaminergic elements in these regions. The present results strongly suggest a dopaminergic control of striatal NT systems and demonstrate that a unilateral loss of this control may lead to strong bilateral alterations in NT levels.