Eosinophil cationic protein (ECP) is probably responsible for the underlying inflammatory mechanisms seen in asthma. It can be modulated in vivo by immunotherapy or steroids, with an appropriate reduction in symptoms of respiratory tract diseases. ECP is an identifiable mediator in additional target organs involved in allergic reactions, making it of potential interest in the study of otitis media with effusion. A qualitative prospective study was designed to discover the relationship of ECP and serum IgE in patients with middle ear effusion and allergy, as demonstrated by RAST and skin testing. The concentrations of ECP in the middle ear fluid from 23 consecutive patients with otitis media with effusion undergoing the placement of tympanostomy tubes ranged from 2 to 1248 micrograms (normal serum ECP, 5 to 15 micrograms), with 87% being abnormally elevated. There was no correlation between an individual's ear and serum levels of ECP (r = 0.1672; p = 0.6232), suggesting a more localized process. There was no relation between effusion ECP and serum IgE (p = 0.0040). ECP from middle ear effusion did correlate with a patient's having allergy, as confirmed by RAST and skin testing (p = 0.0095). Mechanisms involving immune mediated disease in the middle ear, of which the eosinophil may be one participant, are presented.