Immune effector cells were generated in vitro and compared for activity against human head and neck cancer (HNC). A subset of human IL2-activated natural killer (A-NK) cells was able to eliminate tumor cells in vitro by necrosis, apoptosis or cytokine-mediated effects and to induce regression of established tumors in vivo, in a xenograft nude mouse model of HNC. Cytolytic T lymphocytes (CTL) with specificity for a human oral carcinoma were as effective as A-NK cells in mediating killing of autologous tumor cells or entering spheroids. Stable HNC transfectants with the human IL2 gene, which produced IL2 were implanted in nude mice. IL2-secreting tumors regressed spontaneously. Strategies available for use in immunotherapy of human HNC are being evaluated to provide a solid basis for their future therapeutic applications.