Human phagocytic leukocytes express the seven-transmembraneG-protein-coupled receptors formyl peptide receptor (FPR) and FPR-like1 (FPRL1). MMK-1, a synthetic peptide derived from a random peptidelibrary, is reported to induce calcium mobilization specifically inhuman FPRL1 gene-transfected cells. However, its actions onhuman phagocytic leukocytes remain poorly defined. We found that MMK-1is a potent chemotactic and calcium-mobilizing agonist for humanmonocytes, neutrophils, and FPRL1-transfected human embryonic kidney(HEK) 293 cells but is inactive in cells transfected with FPR. MMK-1also activated HEK 293 cells transfected with FPR2, a mousecounterpart of human FPRL1. Furthermore, MMK-1 increasedpertussis toxin-sensitive production of inflammatory cytokines in humanmonocytes. MMK-1 signaling in human phagocytes was completelydesensitized by a well-defined FPRL1 agonist, suggesting thatFPRL1 is likely a receptor that mediates the action of MMK-1 in primarycells. Since MMK-1 is one of the most potent FPRL1-specific agonistsidentified so far, it can serve as a modulator of the hostdefense and a useful agent for further studying the signaling andfunction of FPRL1.