Natural killer (NK) cells express two distinct surface receptors capable of triggering cytolytic effector function. The first is CD16, an immunoglobulin Fc receptor that allows NK cells to mediate antibody-dependent killing (ADCC). NK cells express CD16 in association with zeta, a signal-transducing subunit that is also a component of the T cell receptor complex. Activation of NK cells via CD16 results in tyrosine phosphorylation of zeta. The second NK cell triggering receptor is CD2, a 50-55-kDa cell surface molecule that is also expressed on T cells. Here we show that NK cell activation induced by mAb reactive with CD2 (either anti-T11.1 alone or with anti-T11.2 in combination) also results in the tyrosine phosphorylation of zeta. Our results indicate that CD2 is functionally linked to the CD16-zeta complex and suggest that the zeta subunit plays a central role in the signal transduction pathways utilized by NK cells.