Otitis media with effusion is the most common cause of hearing loss in children today. This report examines the role of immunoglobulin E-mediated hypersensitivity in the development of otitis media with effusion. It is emphasized that immunoglobulin E-mediated hypersensitivity, or allergy, represents only one variable in a very complex disease entity. Bacterial infection, viral infection, and mucociliary clearance are important variables that must be considered and may be effected by the allergic response. On the basis of the world literature and laboratory investigations at the Children's Hospital of Buffalo, it is concluded that otitis media is associated with allergy in 35% to 40% of cases. Furthermore, the middle ear mucosa itself is rarely a target organ for allergy. Release of biologic mediators of inflammation from basophils and mast cells occurs in the nasal mucosa and nasopharyngeal mucosa. These mediators most likely produce eustachian tube edema and inflammation. Over a long period this chronic inflammatory response, along with viral or bacterial infection, produces middle ear effusion.