The website of the Drosophila Genome Project (www.flybase.org) contains the sequence of an annotated gene CG6986, which is predicted to code for a G protein-coupled receptor. We cloned the cDNA of this gene and expressed it in Chinese hamster ovary cells. Screening of a neuropeptide library revealed that the expressed receptor was specific for the neuropeptide proctolin (EC50, 6 x 10(-10) M). Proctolin (RYLPT) was the first invertebrate neuropeptide to be fully sequenced (already in 1975) and occurs with identical structure in both crustaceans and insects, where it has myo- and neurostimulatory actions. Northern blots showed that the Drosophila proctolin receptor was only weakly expressed in embryos, larvae, pupae, and in the thoraces and abdomina of adult flies, but strongly in the heads of adult animals. The Drosophila receptor reported here is the first invertebrate proctolin receptor to be identified. (C) 2003 Elsevier Science (USA). All rights reserved.