Two T4+ cloned T-lymphocyte lines specific for a papain digest product of tetanus toxin are functionally characterized. The two clones were obtained from peripheral blood mononuclear cells activated in vitro by tetanus toxoid, expanded with IL-2, and cloned in soft agar. Both clones could be induced to undergo blastogenesis with tetanus toxoid, tetanus toxin, and the B fragment but not the C fragment of tetanus toxin. In addition, both clones caused cytolysis of plastic adherent cell targets cocultured for 18 hr with either tetanus or the B fragment. Antigen specific proliferation and cytolytic activity were MHC-class I restricted.