The objective of the present study was to identify clinical and laboratory criteria for the chronization of tonsillar pathology and propose methods for immunological rehabilitation of the patients based on the investigations into specific features of the immune response in the oropharyngeal region. A total of 371 patients presenting with chronic tonsillitis (CT) and 54 practically healthy subjects were available for observations. The study materials included saliva samples in which IF-α, IF-y, slgA, IgA, IgG, and IgE levels were measured along with extracellular peroxidase activity (immunoenzyme assay) and palatine tonsil biopsies where lymphocyte subpopulations were identified in the indirect immunofluorescence reaction as well as infection with Epstein-Barr virus, herpes simplex virus, and cytomegalovirus (by PCR). Acute tonsillitis was shown to be accompanied by the activation of antimicrobial local protective factors (interferons, peroxidase system, T- and B-lymphocytes, antibody production). CT in case of infection with Epstein-Barr virus was associated with the deficiency of antiviral and antibacterial protective factors in the oropharynx (interferons, NK-cells, peroxidase activity). The possibility of immune correction using interferons, interferonogens, and bacterial lysate-based preparations is substantiated. The complicated toxico-allergic forms of chronic tonsillitis are shown to develop from the combination of insufficiency of the protective factors (IgG) and the excessive content of IgE. Substitution therapy using antibodies (immunoglobulins for intravenous administration) is proposed as the method of choice for the management of chronic tonsillitis.