Activation studies performed with transfected T cell hybridomas and tumors revealed that chimeric molecules containing the CD3 epsilon or zeta chain intracytoplasmic portions can induce the complete effector functions normally seen only when the complete T cell receptor (TCR)/CD3 complexes of T lymphocytes are triggered. Therefore, the zeta chain, with its three antigen recognition activation motives, is thought to connect the antigen-binding Ti chains with the intracellular signaling machinery of the T cell. Here we demonstrate that the cytoplasmic portion of the TCR-zeta chain is not sufficient to activate resting T lymphocytes when cells from transgenic mice expressing a chimeric zeta receptor are used. However, after (in vivo and in vitro) activation through their endogenous TCR/CD3 complexes, the preactivated T lymphocytes could be triggered through the zeta chimera to the same extent as when they were activated through their endogenous TCR/CD3 complexes. They were able to proliferate and elicit cytotoxic functions when triggered through their zeta chimeras. These results suggest that the triggering requirements for effector functions seem to be different in resting than in activated T cells.