Tumor-infiltrating lymphocytes (TILs) were isolated from surgically excised squamous cell carcinoma of the head and neck. Immunohistology showed that the tumor was infiltrated by T-lymphocytes, many of which were activated as judged by the expression of the following surface antigens: HLA-DR, transferrin receptor, and receptors for interleukin 2 (IL2). Fresh TILs were unable to lyse natural killer cell (NK)-resistant and NK-sensitive tumor cell targets in chromium-release cytotoxicity assays. Tumor-infiltrating lymphocytes as well as autologous peripheral blood lymphocytes were cultured in media containing natural IL-2. Tumor-infiltrating lymphocytes proliferated better than autologous peripheral blood lymphocytes and exhibited sustained growth and antitumor effector function in long-term cultures. The IL2-expanded culture of TILs contained mostly CD8+ (suppressor/cytotoxic) T-lymphocytes with the morphology characteristic of lymphokine-activated killer cells. The ability to expand TILs with augmented antitumor activity in long-term cultures indicates that these cells could be therapeutically useful. Potential application of human TILs to adoptive immunotherapy of squamous cell carcinoma of the head and neck is discussed, and recent advances in immunotherapy with IL2-activated TILs are reviewed.