Cytotoxic T-cell clones have been shown to be capable of killing unrelated target cells in the presence of heteroconjugates consisting of OKT3 (monoclonal antibody against cell surface antigen T3) and targeting antibody. In contrast, human peripheral blood T cells were not known to have this ability, although these cells have been shown to undergo proliferation in response to OKT3 and accessory signals. Here we report that OKT3-stimulated human peripheral blood mononuclear cells effectively killed human melanoma or Raji cells coated with anti-target-cell--OKT3 conjugates. The extent of target-cell killing by stimulated effector cells was much greater than that observed with unstimulated cells, in spite of down-regulation of the T3 structure on the OKT3-treated cells. Target-cell lysis occurred at physiological concentrations of effector cells and was inhibited by monomeric OKT3, indicating that killing was T-cell-mediated.