Directed migration of cells along a chemotactic gradient is a fundamental cellular process involved e.g. in host defense, tissue development, and wound repair. Surprisingly, although a broad spectrum of different mediators are able to induce a chemotactic response, only very few regulators or inhibitors of this function are known. CXCL4 (platelet factor 4; PF4), a platelet-derived CXCchemokine, modulates long-term immunregulatory functions in T cells but lacks the capacity to induce chemotaxis in these cells. However, in the current study we are able to show for the first time, that CXCL4 acts as a potent inhibitor of T cell chemotaxis induced by CXCR3 ligands CXCL11 and CXCL9, but not CXCL10. CXCL4 did neither interfere with ligand binding to CXCR3 nor with ligandinduced internalization or calcium signaling of CXCR3. By several lines of evidence we could rule out the participation of known CXCL4-receptors, like proteoglycans or CXCR3-B, in CXCL4-mediated inhibition of chemotaxis. We, thus, claim the presence of a further, so far unidentified receptor for this chemokine, which is present on T cells. Intriguingly, CXCL4 also reduces the chemotaxis of T cells and neutrophils induced by the CXCR3-independent ligand CXCL12 (SDF-1alpha). Taken together, our results identify CXCL4 as the first chemokine, which acts as an inhibitor rather than an inducer of chemotaxis on T cells and neutrophils in vitro.