In chick brain, specific 2-[ 125I]-iodomelatonin-binding was localized primarily in the visual system, i.e., retinorecipient and relay nuclei and fiber tracts of the tectofugal, thalamofugal, circadian and accessory visual pathways. Unilateral transection of the optic nerve (ONX) significantly reduced the binding of 2-[ 125I]-iodomelatonin (75 pM) in many, but not all, primary retinal targets and visual pathways at 7 and 14 days, but not 1 day, postlesion. As measured using quantitative autoradiography, 2-[ 125I]-iodomelatonin binding was decreased by 90% in both the central portion of the lesioned optic tract and one of its targets, the nucleus of the basal optic root (nBOR). Other retinorecipient areas exhibiting substantial decreases (60%) in 2-[ 125I]-iodomelatonin-binding included the optic tectum, lateroventral and dorsolateral geniculate nuclei and tectal gray area contralateral to the lesion. These findings are consistent with the hypothesis that melatonin receptors are located presynaptically on incoming optic nerve terminals in many retinorecipient areas. This localization may account for most of the binding sites in nBOR. In other primary visual areas, however, melatonin receptors also appear to be located on postsynaptic cells and/or non-retinal afferents. ONX had no significant effect on 2-[ 125I]-iodomelatonin binding in two retinorecipient areas, the visual suprachiasmatic nucleus and the dorsolateral anterior thalamus, which are part of the circadian/oculomotor and thalamofugal pathways, respectively. An unexpected consequence of ONX was that 2-[ 125I]-iodomelatonin binding was decreased in certain secondary (nucleus rotundus, isthmi nuclei) and tertiary level (ectostriatum) nuclei along the prominent tectofugal visual pathway. Binding in the tectorecipient nucleus triangularis was not significantly altered, however. Analysis of secondary level relay nuclei in the oculomotor pathway revealed that binding after ONX was decreased in the ipsilateral Edinger-Westphal nucleus but not in the oculomotor nuclei. Selective transsynaptic changes in 2-[ 125I]-iodomelatonin binding after lesion of the visual input most likely reflect activity-dependent regulation and functional plasticity of central melatonin receptors.