When peripheral blood mononuclear cells (PBMC) were cultured for 5 days with 1000 U/ml of recombinant interleukin-2 (IL-2), lymphokine-activated killer (LAK) cytotoxicity for normal autologous and allogeneic PBMC developed. Autologous PBMC lytic activity was detected in media containing autologous serum and was dependent on the concentration of IL-2 added to the cultures. When purified T lymphocytes, B lymphocytes, monocytes and large granular lymphocytes were compared for their susceptibilities to lysis by autologous LAK, monocytes and B lymphocytes were found to be the most susceptible. In addition, mitogen-induced blasts were more susceptible than unstimulated lymphocytes. Since PBMC cultured in IL-2-containing medium consisted mainly of CD3-positive T lymphocytes and CD16-positive natural killer cells, and since treatment with anti-CD3 monoclonal antibody, but not anti-CD16 monoclonal antibody, reduced LAK activity for normal target cells, T cells appeared to be the effectors for LAK activity in the LAK normal target lysis system.