Surrogate receptor-mediated cellular cytotoxicity against malignant human glioma cells. A method for incorporating palmitate-derivatized antibody molecules into effector cells and the influence of these incorporated antibodies (surrogate receptors) on the lytic potential of peripheral blood lymphocytes is described. This surrogate receptor-mediated cellular cytotoxicity provides a means by which killer cells are directed specifically to the desired target glioma cells. The cytotoxic activity does not require the Fc region of the incorporated antibody molecules and shows more lytic potential than ordinary antibody-dependent cellular cytotoxicity. By complement-mediated cell depletion and Percoll gradient separation, the effector cell populations for surrogate receptor-mediated cellular cytotoxicity are found to be natural killer cells, as in the murine system. This strategy of surrogate receptor incorporation into effector cells may provide not only valuable insights into the mechanism of cell-mediated cytotoxicity, but also a means of generating target-specific effector cells for clinical applications in neurosurgery. 