\s=b\A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha, (T\g=a\-1)produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T\g=a\-1induced only partial remission of the abnormalities. The dose response of T\g=a\-1with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T\g=a\-1and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens. (Arch Otolaryngol Head Neck Surg 1986;112:1185-1190 Therapeutic courses of irradiation are associated with long-lasting depressions of cell-mediated immuni¬ ty (CMI), persisting several months to ten years or more as measured by several assays.14 In studies of CMI in patients with head and neck cancer, the level of immunoreactivity corre¬ lated with the clinical course.59 In these studies, the results of immunoassays before or after treatment cor¬ related with the risk of tumor recur¬ rence and length of survival. Most of the studies utilized cutaneous delayed hypersensitivity to dinitrochlorobenzene and recall antigens as a measure of nonspecific cellular immunity. In patients with clinically localized tumors treated with surgical resec¬ tion, anergy to dinitrochlorobenzene correlated with the incidences of recurrences after treatment.56 In patients treated with radiation thera¬ py, anergy to dinitrochlorobenzene7 and recall antigens8 predicted shortterm survival. The long-lasting immunosuppression after radiation therapy may have relevance to tumor recur¬ rences and second primary tumors in patients with head and neck cancer treated by radiation therapy. These findings give importance to prevent¬ ing or correcting depressions of CMI due to tumor treatment.To quantitate and determine the causes of the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects, a model was developed in C3H mice in which immunosuppression was induced by irradiation via portals limited to either the head and neck or pelvis. Cell-mediated immunity was quantitated by delayed-type hypersensitivity (DTH) to oxazolone using the method of Asher¬ son and Ptak,10 by total peripheral blood lymphocyte counts, by spleen cell counts, and by spleen ...