We present the first 3-D model of the melatonin receptor based on the recently published amino acid sequence of the cloned melatonin receptor. The seven trans membrane helices were positioned using the helices found in the structure of Bacterio Rhodopsine. From the results of an indirect modeling study with six melatonergic agents, an alignment of these compounds was found directing towards common interaction points. These points are suggested to be the two serines in helix three and the histidine in helix five, forming hydrogen bonds with the amide function and the methoxy-oxygen in melatonin, respectively. The ligands were docked into these binding sites and the receptor-ligand complexes were energy minimized. Considering the position of the active and inactive ligands in the receptor and their respective occupied volumes, the structure-activity relationships are rationalized by the suggested model. This model can be of use as a pharmacological test model in molecular biological studies and as a basis to develop compounds being active as synchronizing circadian agents.