CX3CL1/fractalkine is a chemokine with a unique CX3C motif. Fractalkine is synthesized in endothelial cells as a membrane protein, and the N-terminal domain containing a CX3C motif is cleaved and secreted. CX3CR1, the specific receptor for fractalkine, is expressed in monocytes and lymphocytes. Membrane-bound fractalkine works as an adhesion molecule for these leukocytes and the secreted form as a chemotactic factor. Fractalkine is produced by endothelial cells stimulated with tumor necrosis factor-α, interleukin-1 (IL-1), lipopolysaccharide and interferon-γ. Expression of fractalkine in endothelial cells is inhibited by the soluble form of IL-6 receptor-α, 15-deoxy-∆ 12, 14-prostaglandin J2, and hypoxia. The expression of fractalkine is tightly regulated and fractalkine plays an important role in the interaction between leukocytes and endothelial cells. J Atheroscler Thromb, 2004; 11: 15–21.