Otitis media with effusion (OME) is an inflammatory disease of the middle ear cleft. Oxygen free radicals have been implicated in a variety of inflammatory disorders. Oxygen free radicals may also be involved in the pathogenesis of OME. To evaluate the involvement of oxygen free radicals in the pathogenesis of OME, the level of malondialdehyde, which gives an index of lipid peroxidation by oxygen free radicals, was measured by the reaction with thiobarbituric acid. Malondialdehyde level in the middle ear fluid from the OME group was higher than that in the normal control group. Malondialdehyde level in the middle ear fluid from a mucoid subgroup was higher than that in the serous subgroup. Malondialdehyde levels in the middle ear fluid from the serous subgroup was significantly correlated with symptom duration. The Pearson correlation coefficient between malondialdehyde levels in the middle ear fluid from the serous subgroup and symptom duration was 0.842 (P<0.05). These results indicate that lipid peroxidation by oxygen free radicals may be involved in the pathogenesis of human OME.