The kisspeptins are KiSS-1 gene-derived peptides which signal through the G protein-coupled receptor 54 (GPR54), and have recently been shown to be critical regulators of reproduction. Acute intracerebroventricular (ICV) or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary gonadal (HPG) axis. This effect is thought to be mediated via the hypothalamic gonadotrophin-releasing hormone (GnRH) system. Chronic administration of GnRH agonists paradoxically suppresses the HPG axis following an initial agonistic stimulation. We investigated the effects of continuous peripheral kisspeptin administration in male rats using Alzet® minipumps. Initially we compared the effects of acute subcutaneous (SC) administration of kisspeptin-10, -14 and -54 on the HPG axis. Kisspeptin-54 produced the greatest increase in plasma luteinizing hormone (LH) and total testosterone at 60mins post injection and was used in the subsequent continuous administration experiments. Chronic SC long-term administration of 50 nmol kisspeptin-54/day for 13 days decreased testicular weight. Histological examination showed degeneration of the seminiferous tubules associated with a significant decrease in the circulating levels of the testes-derived hormone, inhibin B. Plasma free and total testosterone were also lower, although these changes did not reach statistical significance. Further studies examined the effects of shorter periods of continuous kisspeptin administration. SC administration of 50 nmol kisspeptin-54 for 1 day increased plasma LH and testosterone. This effect was lost following 2 days of administration, suggesting a down regulation of the HPG axis response to kisspeptin following continuous administration. These findings indicate that kisspeptin may provide a novel tool for the manipulation of the HPG axis and spermatogenesis.