Insect growth through multiple developmental stages depends on successful completion of ecdysis, a stereotypic physiological sequence under hormonal control. The patterned behaviors performed during ecdysis are programmed in the central nervous system and activated by ecdysis triggering hormones (ETHs). As a first step in defining the cellular substrates underlying ecdysis behaviors, we have identified ETH receptors in Drosophila and Manduca. The Drosophila gene CG5911 encodes two functionally distinct subtypes of G protein-coupled receptor through alternative splicing (CG5911a and CG5911b) that respond preferentially to ETHs of flies and moths. The CG5911 ortholog in Manduca also encodes two splice variant GPCRs (MasETHRa, MasETHRb) quite similar to Drosophila counterparts in structure and pharmacological profile. In situ hybridization using DNA probes specific for the two receptor subtypes reveals mutually exclusive patterns of neuronal staining in the CNS. These data are consistent with a direct action of ETH on strategic neuronal targets of the CNS with diverse functions.