We have cloned from brain, ovary and eggs of the cephalopod Sepia officinalis a 269-bp PCR product, which shares 100% sequence identity with the open reading frame of GnRH isoform isolated from Octopus vulgaris. Similar to Octopus, this sequence encodes a peptide that is organized as a preprohormone from which, after enzymatic cleavage, a dodecapeptide is released. Apart from its length, this peptide shares all the common features of vertebrate GnRHs. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses followed by sequencing have confirmed that the same peptide transcript is also present in the ovary, as well as in eggs released in the mantle cavity. The use of an antibody made specifically against the oct-GnRH has revealed that the peptide is localized in the dorso-lateral basal and olfactory lobes, the two neuropeptidergic centers controlling the activity of the gonadotropic optic gland. Immunoreactive nerve endings are also present on the glandular cells of the optic glands. These results confirm the fact that, regardless of the evolutionary distances among animal phyla, GnRH is an ancient peptide present also in invertebrates, and also reinforce the notion that, despite the name "gonadotropin releasing-hormone" was attributed according to its role in vertebrates, probably this family of peptides always had a role in the broad context of animal reproduction. The divergence and spread of several different isoforms of this peptide among animals seem to be balanced, in both invertebrates and vertebrates, by the class-specificity of the GnRH isoform involved in reproductive processes.