Using oligonucleotide probes derived from consensus sequences of known vertebrate and invertebrate G protein-coupled receptors, we have cloned the cDNA for a presumed G protein-coupled receptor from sea anemones. This receptor shows a striking structural homology with members of the glycoprotein hormone (FSH, TSH, LH/CG) receptor family from mammals, including a very large, extracellular N terminus (18-25% sequence identity) and a 7 transmembrane region (44-48% sequence identity). As with the mammalian glycoprotein hormone receptor genes, the sea anemone receptor gene yields transcripts which can be alternatively spliced, thereby yielding a shortened receptor variant only containing the large extracellular (soluble) N terminus. All this is strong evidence that the putative glycoprotein hormone receptor from sea anemones is evolutionarily related to those from mammals. This is the first report showing that a putative glycoprotein hormone receptor occurs in invertebrates.