Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized. We report chemotaxis and competitive binding studies that show LEC binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L. A neutralizing polyclonal antibody to LEC was developed to demonstrate that the unusually high concentration of LEC required to induce chemotaxis was a property of LEC and not as a result of an irrelevant protein contamination. This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration.