NK cells are present mostly in blood and spleen but under certain pathological and physiological conditions rapidly accumulate at extrahematic sites. The present study investigates the responsiveness of NK cells to C-C chemokines and the mechanisms of emigration from the bloodstream. MCP-1 induced migration across polycarbonate filters of IL-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. The related chemokines MCP-2 and MCP-3 were also active. IL-2-activated NK cells showed specific binding sites for labeled MCP-1, and cell migration was inhibited by both cholera and Bordetella pertussis toxins. In agreement with functional assays the expression of mRNA specific for MCP-1 receptors was detectable only in IL-2-activated NK cells. The ability of NK cells to respond to MCP-1 and related chemokines may be one important determinant of NK cell emigration and recruitment in tissues.