Calcitonin and corticotropin-releasing hormone (CRH) are members of a family of neuropeptides that exert effects by activating secretin-type G-protein coupled receptors. Calcitonin lowers blood calcium levels and acts to protect against calcium loss from the skeleton during periods of calcium mobilisation. CRH is a key player in the stress response mediated by the hypothalamic-pituitary-adrenal axis. Analysis of the phylogenetic distribution of calcitonin-type and CRH-type peptides and their receptors indicates that the evolutionary origin of these signalling systems can be traced to the common ancestor of the Bilateria. Furthermore, it has been discovered that calcitonin-type and CRH-type peptides act as diuretic hormones in insects. However, little is known about the physiological roles of these peptides in other invertebrates. We are using the starfish Asterias rubens (phylum Echinodermata) as a model system to investigate the evolution and comparative physiology of neuropeptides. As deuterostomian invertebrates, echinoderms bridge the evolutionary gap between protostomian invertebrates (e.g. insects) and the vertebrates. Furthermore, the pentaradial symmetry of echinoderms provides a unique context for investigation of neuropeptide function. Here we report the cloning and sequencing of cDNAs from A. rubens that encode a calcitonin-like peptide precursor (ArCTLPP) and CRH-like peptide precursor (ArCRHLPP). Analysis of the expression of these precursors in A. rubens using mRNA in situ hybridisation revealed that ArCRHLPP is expressed by cells in the ectoneural region of the radial nerve cords and circumoral nerve ring, marginal nerves, coelomic epithelium, cardiac and pyloric stomach and pyloric caecae, whilst ArCTLPP is expressed in the ectoneural and hyponeural regions of the radial nerve cords and circumoral nerve ring, cardiac and pyloric stomach and pyloric caecae. These data provide a basis for investigation of the physiological roles of calcitonin-type and CRH-type neuropeptides in starfish, which may provide novel insights on the evolution of neuropeptide function in the animal kingdom.