Chemokines are considered important mediators of various inflammatory processes. In human basophils, different CC chemokines are known to stimulate release of histamine and generation of leukotriene (LT)C-4. In the present study, we have evaluated the effect of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta on mast cell activation. Whereas all these CC chemokines caused dose-dependent release of histamine from basophils in mixed human leukocyte suspensions, none of them was able to induce release of histamine as well as tryptase or prostaglandin (PG)D-2 from human skin mast cells, nor did priming with these substances enhance IgE-mediated mediator release. In addition all chemokines failed to promote changes in the cytosolic free calcium level in the human mast cell line HMC-1. These results add further evidence for the differences between human mast cells and basophils regarding cytokine-dependent activation.