Calcitonin is a key hormone involved in the regulation of calcium metabolism in vertebrates. Using oligonucleotide primers derived from consensus sequences of vertebrate calcitonin receptors, we have cloned and characterized the first representative of an invertebrate calcitonin receptor from the bivalve mollusc Crassostrea gigas. This receptor named Cg CT-R exhibits 39% amino acid sequence identity with both human calcitonin and calcitonin gene-related precursor receptors. Cg CT-R is expressed mainly in the gills and the mantle edge as well as at lower levels in muscles, digestive gland, heart, and labial palps. Transfer of animals from seawater to brackish water resulted in a significant decrease of Cg CT-R transcript levels in the gills, thus suggesting a role for ionic balance in molluscs.