Melatonin is a neurohormone synthesized and secreted mainly during the dark period of the circadian cycle by the pineal gland. It has already been proved to be involved in a number of chronobiological processes, most of them being mediated by its membranar receptors MT1and MT2. Both are members of the GPCR class and, despite the interest they elicit, their 3D structure is still to be described. Models for both human MT1and MT2receptors have been constructed by homology modeling, using the X-ray structure of bovine rhodopsin as template. These models have been evaluated in terms of hydrophobic properties of the helices and refined to take into account the rearrangement of GPCRs necessary for their activation, thus leading to a putative activated model for each subtype. © 2007 Elsevier Masson SAS. All rights reserved.