Leukotactin-l (Lkn-l )/CCL15 has been known as a potent chemoattractant of leukocytes. However, the precise function of Lkn-l in human neutrophils has not been explained well. In the present study, we investigated the contribution of Lkn-1 in chemotactic activity of human neutrophils. Both CCR1 and CCR3 mRNA expressions are strongly expressed in human neutrophils but CCR2 protein expression was uniquely detected on the cell surface. Lkn-l binding to CCR1 and CCR3 induced chemotactic activity of neutrophils. Chemotactic index of Lkn-l was comparable to that of IL-8. $MIP-1{alpha}/CCL3$ binding to CCR1 and CCR5 has no effect on neutrophil migration. Cell migration, in response to Lkn-l, was blocked by pertussis toxin (Ptx), a $G_o/G_i$ protein inhibitor, and U73122, a phospholipase C(PLC) inhibitor but not by protein kinase C inhibitor such as rottlerin, and Ro-31-8425. Taken together, our results demonstrate that Lkn-l transduces the chemotaxis signal through $G_o/G_i$ protein and PLC. This finding provides the molecular mechanism by which Lkn-l may contribute to neutrophil movement into the site of inflammation.