A series of 84 patients with carcinoma of the larynx or hypopharynx was studied with regard to tumor host interaction. Prognostic evaluation of the “tumor” aspects of this interaction included preoperative staging (TNM), histologic grading of the primary tumor, and histologic examination for the presence of metastases confined to regional lymph nodes or extranodal spread. Morphological evidence of host resistance was judged by the presence and degree of lymphoid inflammatory infiltration around the primary tumor and factors suggestive of enhanced immune reactivity in lymph nodes, i.e., sinus histiocytosis, germinal center hyperplasia, plasmacytosis, and the presence of pyroninophilic blast cells. Of the factors evaluated, those which appeared to correlate best with 5-year survival were stage of disease, presence or absence of positive regional nodes, histologic grade of the primary tumor, lymphoid infiltration in the primary tumor, and extensive germinal center hyperpiasia in the regional nodes. The favorable prognosis attached to the presence of lymphoid infiltration or germinal center hyperpiasia, however, was not uniform for all patients. The presence of lymphoid infiltration was a favorable sign only in the group of patients with positive nodes or in those patients with well-differentiated (Grade I, II) tumors. The presence of extensive germinal center hyperpiasia was a favorable prognostic sign only in those patients with positive nodes or in those patients who had a poorly differentiated (Grade III, IV) tumor. None of the other morphological structures related to lymph node reactivity showed favorable prognostic significance. The relationship of morphology to host immune mechanisms was discussed.