Leptin regulates the hypothalamo-pituitary-gonadal (HPG) axis in relation to nutritional status. The mechanism through which leptin mediates its effects on neuroendocrine reproductive circuits remains unclear. Galanin-like peptide (GALP) is a recently identified hypothalamic peptide, localized in the arcuate nucleus, which appears to be regulated by leptin and stimulates LH when administered centrally. Here we demonstrate that leptin stimulates the release of GALP and gonadotropin-releasing hormone (GnRH) in vitro from hypothalamic explants harvested from male rats. In addition we show that GALP stimulates the release of GnRH from hypothalamic explants and GT1-7 cells. Furthermore we demonstrate GALP antiserum blocks the stimulatory action of leptin on GnRH release from hypothalamic explants. GALP is a ligand of the galanin receptors. We therefore investigated whether the effect of GALP on GnRH release may be mediated via a known galanin receptor. GALP-stimulated GnRH release from hypothalamic explants was attenuated, but not abolished by the galanin receptor antagonist galantide. However GALP-stimulated GnRH release from GT1-7 cells was not diminished by the co-administration of galantide. In addition none of the cloned galanin receptors were expressed in GT1-7 cells by RT-PCR. These observations suggest GALP may stimulate GnRH release through an indirect pathway involving a galanin receptor and via a direct action on GnRH neurons, possibly through a novel receptor. These findings suggest GALP may mediate the actions of leptin on the reproductive axis and provide a link between nutrition and fertility.