A total of 63 patients with advanced untreatable stage III and IV head and neck cancers were investigated for clinical responses and immunologic reactivities before and during S2-complex treatment.Data of the immunological parameters were compared with those of healthy age-matched controls. Patients population consisted of 26 patients with carcinoma of larynx (41.2 %) , 11 with nasopharynx (17.4 %) 11 with hypopharynx(17.4%). The remaining patients were presented with Parotid gland tumor carcinoma of the tongue, cheek, skin, retromolar,region,tonsils maxillary sinus , upper alveolar ridge, posterior pharyngeal wall and unknown primary tumor S2-complex induced 7.9 % complete responses at 2 months,9.5% at 4 months and 11.1 % at 6 months . Partial responses at 2,4 and 6 months were 28.5 %,11.1% and 9.5% respectively, Stable disease levels were 7.9 % ,7.9 % and 3.1 % at 2,4 and 6 months respectively While the progressive disease rate, at 2 and 4 months were 6.3 % and 6.3 % respectively and at 6 months no patients with progressive disease were remained , Carcinoma of the larynx was the most responsive site with respect to S2- complex treatment . The immuriological parameters revealed that the mean total leukocyte counts in head and neck cancer patients before treatment was significantly higher than control Absolute neutrophil counts were also significantly higher than those of the controls while the absolute lymphocyte numbers were lower in patients than those of the controls S2-complex treatment brought no significant alteration in these parameters in comparison with the pretreatment levels On individual basis „ however , the number of patients with depressed total lymphocytic counts dropped from 17/63 (26.9%) in the pretherapeutic period to 1/15 (6.6 %) after 6 months of therapy . T and B-cell counts and percents before treatment were significantly lower than those of healthy controls.S2-compleex treatment resulted in immunorestoration of these indices to healthy human normal ranges after 2 weeks of treatment . Long term therapy too caused maintenance of these restored immune responses.On individual basis , however . the number of patients with depressed T-lymphocytes decreased from 28/63 (44.4%) before treatment to 1/15 (6.6 %) at 6 months of therapy.In respect to B-cells . number of patients with suppressed levels were shifted from 41/63 (65%) it pretherapeutic treatment period to 5/15 (33.3 %) at 6 months period . T-lymphocyte subsets before S2-complex treatment were asi follows : CD8 % was normal while CD4% was low, CD4/CD8 ratio was only slightly depressed and the HLA-DE (la) positive cells were high in comparison to that of healthy controls . Short and long term S2-complex treatment resulted in restoration of CD4. levels . enhancement of CD2 cells, HLA DR positive cells and profound inversion of CD4/CD8s ratio . Autoantibodies at the pretreatment period were those directed against nuclear,thyroid microsomal , epithelial cells , gastric parietal cells smooth muscles,leukocytes,T-cells, B-cells,monocytes,thymus reticular tissues and Hassall's corpuscles.Besides , antibodies at low incidences towards glomerular basement membrane and vascular endothelial tissues were demonstrated. A transient polyclonal activation after short term S2-complex treatment was noticed in the autoantibodies directed to nuclear , thyroid microsomal,epithelial,parietal cell,smooth muscles thymocytes Freticular cells , Hassall's corpuscles. Later on, however at 6 months of follow-up most autoantibody responses were returned to normal healthy control levels. Except for the incidence of anti-glomerular basement membrane and antiendothelial antibodies which remained high at 6 months of s2-complex therapy . Autoantibodies specific to mitochondrial, thyroglobulin and red blood cells were only occasionally detected in head and neck cancer patients before and after S2-complex treatment . Correlation between clinical responses (complete response . partial response , stable disease and progressive disease) of the head and neck cancer patients and the following immunological parameters were demonstrated : while blood cell count , neutrophil percent lymphocyte percent and counts , CD4, percents , CD8 percents CD4/CD8 ratio and HLA-DR(la) positive cells percents total T-cells and lymphocytes percent and counts were generally helpful at predicting clinical responses