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The role of allergy in chronic otitis media with effusion (OME) is controversial. New evidence from cellular biology and immunology explain the basics of allergic reactions and allow more accurate diagnosis of allergies and inflammatory disease throughout the unified airway. This article examines the epidemiologic, methodological, and immunologic studies of allergic causes of OME, including (1) evidence for and against OME as an allergic disease, (2) allergy as a cause for eustachian tube obstruction, (3) examination of the most sensitive diagnostic tests for allergy, and (4) the effect of treatment of underlying allergies in improving and resolving middle ear disease.