A murine model for the immunotherapy of head and neck cancer was established. The AT-84 tumor, a spontaneously arising oral squamous cell tumor of C3H mice, was evaluated for susceptibility to lymphokine-activated killer (LAK) cells. In vitro chromium-release assays demonstrated that AT-84 is sensitive to LAK-cell-mediated killing. Furthermore, in vivo experiments employing a lung metastasis model demonstrated a 50% reduction in the number of metastases in LAK-cell-treated mice as compared with untreated controls (P2 = .001). These experiments showed that AT-84 is an appropriate model for the immunotherapy of head and neck cancer. This model should be invaluable for further study of the mechanisms involved in immune-mediated therapy of head and neck cancer.