Monocyte Chemotactic Protein(MCP)-1 and other members of the C-C branch of the chemokine superfamily (RANTES, MIP1 alpha/LD78, and MCP-3) induced, at chemotactic concentrations, the release of [3H]arachidonic acid in prelabeled human monocytes. Arachidonate release was potentiated (2 to 4 fold) in the presence of platelet activating factor (PAF). PAF effect was blocked by a specific receptor antagonist, WEB 2187, and was not present when inactive analogs, PAF inactive enantiomer, or lysoPAF were used. Thus, the synergistic action of PAF with C-C chemokines, in terms of arachidonate release and chemotaxis, is specific for this alkylphospholipid and is receptor mediated. Reciprocal potentiation of PAF and C-C chemokines may be important at sites of inflammation.