It has been established that patients with cancer of the head and neck region generally exhibit immunosuppression, even at the early stages of the disease. Immunosuppression has been found in tests performed in vitro. However, in vitro assays do not adequately reflect in vivo immune status. Upon activation, lymphocytes release a soluble form of interleukin-2 receptor(IL-2R). Increased serum levels of soluble IL-2R have been noted in a variety of lymphoproliferative disorders and in conditions associated with active T-cell responses. Activated T-cells also release an interferon-gamma that is capable of activating, in macrophages, a guanosine triphosphate(GTP) cyclohydrolase leading to increased synthesis and excretion of neopterin. Since soluble IL-2R and neopterin can be utilized as markers for the clinical assessment of cell-mediated immune responses, we studied the occurrence of elevated soluble IL-2R and neopterin levels in sera from patients suffering from head and neck squamous cell carcinoma. Moreover, we explored whether soluble IL-2R and neopterin serum levels reflect progress of the disease. Levels of Soluble IL-2R were measured with an enzyme immunoassay, and serum levels of neopterin were measured with radioimmunoassay. T₄, T₈ and total T lymphocytes were measured using immunobead analysis. The following results were obtained : 1) T₄/T₈ cell ratios in patients with head and neck squamous cell carcinoma were significantly higher than normal. However, the percentage of total T lymphocytes in the peripheral blood of patients with head and neck squamous cell carcinoma did not vary from the control. T-cell counts and T₄/T₈-cell ratios were not correlated with the stage of the tumor. 2) Mean values of soluble IL-2R and neopterin were significantly higher in head and neck squamous cell carcinoma patients than in healthy controls(P<0.01). 3) Elevations in serum soluble IL-2R and neopterin were correlated with the stage of the tumor in patients with head and neck squamous cell carcinoma. These data indicate that primary events in the immune surveillance are intact in patients with head and neck squamous cell carcinoma but effector mechanisms may be diminished. An activation of cell-mediated immunity appears to be persistent in the all patients with head and neck squamous cell carcinoma and the level of activation seems to be parallel with the stage of tumor.