Suprachiasmatic nuclei (SCN) and pars tuberalis (PT) are two structures in the rat exhibiting high affinity receptors for melatonin. Melatonin receptor density in these two structures was previously shown to be inversely related to endogenous ligand concentration, thus elevated at daytime. We now demonstrate that, in the PT, these daily variations are directly induced by the circadian rhythm of plasma melatonin concentration. Variations persist in constant darkness and can only be blocked by pinealectomy. Thus, autoregulation loop of melatonin receptors determines the circadian rhythm in PT melatonin receptor density. However, this process of desensitization does not determine the daily variations in SCN melatonin receptor density. Indeed, in the SCN, the light/dark cycle is the regulatory factor: melatonin receptor density was shown to be specifically reduced during the night even in pinealectomized animals, while one h light was shown to reverse this nocturnal decrease in the SCN. Moreover, this darkness-induced down-regulation of SCN melatonin receptors has a masking effect on the earlier shown ligand-dependent desensitization process in this structure. This explain why, in constant darkness, SCN melatonin receptor density did not show any variation throughout the 24 h subjective day and night, although the circadian rhythm of melatonin persisted. These results thus clearly show that although daily rhythms in the density of melatonin receptors are identical in the PT and in the SCN, their regulation is totally different in each of these two structures.