The action of antibacterial cathelicidin peptide CAP11 on the anandamide production from mononuclear phagocytes was examined. Lipopolysaccharide (LPS)-stimulation induced the anandamide production from macrophage-like RAW264.7, accompanied with the enhanced anandamide-synthesizing enzyme activity; however, the anandamide-degrading enzyme activity was not changed by LPS-stimulation. Importantly, CAP11 suppressed the LPS-induced anandamide production and the increase of anandamide-synthesizing enzyme activity. Furthermore, CAP11 abrogated the LPS-binding to CD14-positive RAW264.7. These observations indicate that CAP11 inhibits the binding of LPS to CD14-positive mononuclear phagocytes, thereby suppressing the anandamide synthesizing enzyme activity and the anandamide production from the cells.