The neuropeptide FLFQPQRF amide is a FMRFamide-like peptide with some anti-opiate properties. Neuropeptide FLFQPQRFamide receptors are present in the mammalian central nervous system and have been clearly identified as different from opiate receptors. Autoradiography has revealed neuropeptide FLFQPQRFamide receptor localization within the ventral mesencephalon, where opiate receptors are also located. In order to delineate anatomical localization of neuropeptide FLFQPQRFamide receptors, we used selective chemical lesions of dopaminergic cells and intrinsic perikarya of the ventral mesencephalon, coupled with in vitro autoradiographic techniques. We show that: (i) unilateral lesions of dopaminergic perikarya produced by 6-hydroxydopamine did not affect either ipsi or contralateral neuropeptide FLFQPQRFamide receptor density within the mesencephalon; (ii) unilateral lesions of intrinsic perikarya by ibotenic acid injected into the ventral tegmental area produced a significant reduction of neuropeptide FLFQPQRFamide receptors (40%) in this region; (iii) in the substantia nigra pars compacta, ibotenic acid unilateral lesions did not affect the density of neuropeptide FLFQPQRF-amide receptors; (iv) unilateral 6-hydroxydopamine or ibotenic acid lesions failed to affect neuropeptide FLFQPQRFamide binding in the dopaminergic projection areas. These results suggest that, like opiate receptors, the neuropeptide FLFQPQRFamide binding sites are not localized on dopaminergic neurons but are distributed on both soma of non dopaminergic cells in the ventral tegmental area and on fibers afferent to the ventral tegmental area and substantia nigra pars compacta. To evaluate the possibility that the stimulation of neuropeptide FLFQPQRFamide receptors may affect the opioid modulation of mesocorticolimbic dopaminergic neuron activity, we tested the effects of neuropeptide FLFQPQRFamide ventral tegmental area infusion (0.25-10 micrograms) on the behavioral activation induced by intra-ventral tegmental area morphine infusion. We observed that in the ventral tegmental area, the stimulation of neuropeptide FLFQPQRFamide receptors inhibits morphine-induced locomotor hyperactivity. These results suggest that in the ventral tegmental area, neuropeptide FLFQPQRFamide may participate, via an indirect mechanism, to the control of the mesocorticolimbic dopaminergic system activity by counteracting the effect of opioids.