Reproductive function depends on the stimulatory action of gonadotropin-releasing hormone (GnRH), secreted by the brain. Original work in birds identified and isolated a peptide that inhibits gonadotropin release, named gonadotropin inhibitory hormone (GnIH). There is no evidence for a similar factor operant in mammals. This mammalian orthologue of GnIH has been named RFamide-related peptide (RFRP), and negatively regulates GnRH function and gonadotropin secretion. In particular, mammalian GnIH inhibits the function of GnRH cells and acts at the level of gonadotropes. It appears to play a major role in seasonal regulation of reproduction and also to be involved in regulation of stress and food intake.