Ghrelin is a 28 amino-acid peptide that has been shown to induce positive energy balance when administered both peripherally and centrally. This effect appears to occur by increasing food intake and by reducing fat utilization. Ghrelin injected into the PVN increases food intake dose-dependently. The NPY receptor has been implicated in the orexigenic effect of ghrelin, but until now, the role of melanocortins on the effect of ghrelin in the PVN has not been reported. Sprague–Dawley rats were stimulated to eat by PVN ghrelin. Pre-injection of 10 pmol of MT II into the PVN caused a significant decrease in ghrelin-induced feeding in both 0–1 h and 0–4 h food intake studies. This finding indicates that MC 3/4-R signaling appears to be recruited by ghrelin, in the PVN, in its role to induce feeding.