Twenty three naphthalenic bio-isosteres of melatonin have been synthesized. The main structural variations concerned the acylamino substituents of the side chain and the alkoxy group on the 7-position of the naphthalene. Some of these compounds show greater affinity than melatonin itself for the melatonin receptor. The results of this study provide new informations on the structure affinity relationships and on the mode of interaction at the melatonin binding site.