The role of the immune system in the pathogenesis and treatment of cancer remains to be determined. Impairment of humoral and cellular immunity has been associated with various factors implicated in head and neck cancer--tobacco, alcohol, and malnutrition. Whether these immune dysfunctions are causative or a secondary effect is not known. Patients with head and neck cancer have well-documented defects in immune function. In general, depression in cellular immunity has been noted, which can be correlated with stage of disease and prognosis. Conversely, increased humoral immune responses are seen, especially salivary IgA and circulating immune complexes. It may be that IgA or immune complexes are capable of suppressing the cellular immune response. Clinical trials utilizing biologic response modifiers in head and neck cancer have begun. Preliminary studies with heavily pretreated patients have demonstrated antitumor activity, suggesting that immunotherapy may provide a treatment alternative. In conclusion, the weight of evidence suggests that the immune response to head and neck cancer does play a role in the pathogenesis of the disease. A better understanding of the host-tumor interaction will allow for improved utilization of biologic response modifiers in the treatment of head and neck cancer.