The CXC chemokine stromal derived factor-1alpha (SDF-1alpha) induces both the chemotaxis and calcium mobilization in IL-2-activated NK (IANK) cells. The ability of SDF-1alpha to induce IANK cell chemotaxis is inhibited upon incorporating antibodies to the alpha subunit of Go and Gq but not Gi, Gs, or Gz, whereas (Ca++)i mobilization is inhibited with anti-Go, [corrected] anti-Gq and anti-Gs, but not with any other anti-G proteins examined. Further analysis showed that antibody to phospholipase C (PLC)beta but not PLCgamma inhibited SDF-1alpha-induced (Ca++)i mobilization, suggesting that this signal is mediated by G protein coupled receptor and not by tyrosine kinase receptors. Our results are the first to show that SDF-1alpha is chemoattractant for NK cells, and that this effect is coupled to G proteins.