The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides were demonstrated in the nervous systems of all classes of coelenterates. Using a radioimmunoassay for RFamide, three such peptides were isolated from the sea anemone Anthopleura elegantissisma and sequenced: less than Glu-Gly-Arg-Phe-NH2 (Antho-RFamide), less than Glu-Ser-Leu-Arg-Trp-NH2 (Antho-RWamide I) and less than Glu-Gly-Leu-Arg-Trp-NH2 (Antho-RWamide II). The general structure of these peptides can be described as less than Glu...Arg-X-NH2, where X is an aromatic amino acid. From the hydromedusa Polyorchis penicillatus, the peptide less than Glu-Leu-Leu-Gly-Gly-Arg-Phe-NH2 (Pol-RFamide I) was isolated, which also belongs to the less than Glu...Arg-X-NH2 family. Using specific antisera it was shown that all four peptides were located in neurones. Application of low doses of Antho-RFamide, or Antho-RWamide I or II induced contractions of endodermal muscles of sea anemones. This indicates that these neuropeptides play a role in neurotransmission.