The mandibular closer muscles of the cricket, Gryllus domestica, contain a 5-hydroxytryptamine (5-HT)-sensitive receptor that is coupled to adenylate cyclase. A structure-activity study of the 5-HT molecule indicates that the integrity of the ethylamine sidegroup and the presence of a negatively charged moiety at the 5 position (-OH, -OCH3) are essential for activity. A pharmacological profile is presented for this receptor. The receptor differs from any reported mammalian 5-HT receptor in that none of the mammalian agonists tested were effective. However, the mammalian antagonists for 5-HT receptors, spiperone, mianserin, and ketanserin as well as the anti-histaminic cyproheptadine were all effective antagonists in this preparation. Preliminary analysis of antagonism, particularly by spiperone, shows that these antagonists are probably acting non-competitively. On the basis of the pharmacological data, and comparisons with other insect systems, the 5-HT receptor present in the cricket mandibular muscles has been tentatively classified as 5-HT2-like.