Metastatic squamous cell head and neck cancer was treated in four patients with low-dose cyclophosphamide (to reduce suppressor T-cell activity), indomethacin (to reduce prostaglandins that mediate macrophage-induced immune suppression), zinc (to augment T-cell function via thymulin), and mixed natural interleukins perilymphatically in the neck (as adjuvant for tumor antigen in the region). Three patients responded within 7 days with major tumor regressions progressive during the period of treatment and associated with increased infiltration with lymphocytes and tumor cell lysis. Two showed histologic features of intense delayed hypersensitivity with granulomatous changes. The fourth patient was anergic and failed to respond clinically. Tumor-specific immune response, despite preexisting immunodeficiency, is postulated as the mechanism of the responses in these patients.