The aim of this study was to investigate the involvement of histamine H1 receptors in the amylin-leptin interaction using H1rKO mice. Compared with WT controls, 4-5 months old H1rKO mice had a significantly higher body weight, higher amount of fat mass and higher leptin levels; amylin and insulin levels were unchanged. No significant differences were detected in energy expenditure (EE), respiratory quotient or physical activity; however, H1rKO mice showed a tendency toward decreased EE. Food intake (FI) after a 6-hour fast was significantly higher. H1rKO mice were less responsive to amylin and leptin injections unless very high doses were used. Interestingly, the amylin-induced activation of neurons in the area postrema and the leptin-induced activation of hypothalamic nuclei were not affected, thus the reduced amylin and leptin action in H1rKO mice may not be due to the insensitivity at their primary brain sites. Finally, WT mice showed reduced FI after the combined amylin-leptin treatment, but H1rKO did not respond. With this study we showed that the lack of H1 receptors markedly reduced the anorectic effect of amylin and leptin. Since the primary responding brain areas were still responsive, as indicated by cFos and pSTAT3 signaling, the dysfunction of signaling seems to lie in the respective downstream pathways. Ziel der Arbeit war es, den Einfluss von Histamin H1 Rezeptoren auf die Interaktion von Amylin und Leptin bei H1rKO Mäusen zu untersuchen.