Natural killer (NK) cells are a subset of lymphocytes that mediate major histocompatibility complex (MHC)-nonrestricted cytotoxicity against tumours and virus-infected cells and secrete numerous cytokines on activation. NK cells are distinct from mature T lymphocytes, because they do not rearrange or productively transcribe T-cell receptor alpha-, beta-, gamma- or delta-chain genes and do not express the CD3 gamma- or delta-subunits. But recent studies indicate that NK cells do express CD3 zeta, co-associated with other membrane proteins. Here we report that CD16, the receptor for the Fc (constant) region of IgG, specifically associates with the CD3 zeta homodimer on the membrane of human NK cells, and that co-transfection with CD3 zeta complementary DNA permits expression of a transmembrane-linked CD16 complex on COS-7 cells. These findings indicate that CD3 zeta can co-associate with membrane receptors of diverse cell types and function as a common structure for signal transduction.