To determine whether or not stimulations of various inflammatory irritants such as endotoxin and/or immune complexes (IC) play a role in the pathogenesis of otitis media with effusion (OME), experimental animal models were examined under light and electron microscopy. Horseradish peroxidase (HRP) was chosen as an antigen and anti-HRP sera were obtained from the animals immunized by emulsions of HRP and Freund's complete adjuvant. Seventy-three albino guinea pigs and 41 chinchillas were used in this experiments. One hundred and fourteen animals were divided into three groups: forty in the active Arthus (AA) group, 61 in the passive Arthus (PA) group and 13 in the control group. According to the chronological changes of the tympanograms, it was confirmed that the pathological changes in the middle ear cleft of the OME animals persisted for at least 10-14 days after the injection, whereas those in the control animals recovered within 3-4 days. Histological examinations of both PA- and AA-group animals revealed that electron-dense HRP-positive cells, most of which were non-ciliated, were widely dispersed in the epithelium. Many inflammatory cells such as polymorphonuclear leukocyte (PMN), macrophage and plasma cells were seen in the lamina propria and some PMNs were attached to the basal lamina. Intra-epithelial infiltration of PMNs and epithelial cell degeneration associated with the disrupted basal lamina were also observed. Most conspicuous changes were found in the Eustachian tube.(ABSTRACT TRUNCATED AT 250 WORDS)