Fresh suspensions of tumor-infiltrating lymphocytes (TIL) from 16 patients with squamous cell carcinoma of the head and neck (SCCHN) were examined for T-cell markers including CD4 (helper-inducer), CD8 (cytotoxic-suppressor), natural killer (NK) cell, and activation surface markers using monoclonal antibodies and two-color flow cytometry. Two of 8 (25%) patients with a CD4/CD8 ratio of less than 1 developed cervical lymph node metastases; none had extracapsular spread. Six of 8 (75%) patients with a CD4/CD8 ratio of greater than 1 developed cervical metastases; 5 of 6 (83%) exhibited extracapsular spread. An increased CD4/CD8 ratio was attributable to a decrease in CD8+ cells. A CD4/CD8 ratio of greater than 1 may be a useful prognostic indicator of the development of cervical metastases.