Oxygen free radicals (OFRs) have been implicated in the pathogenesis of an increasing number of diseases and inflammatory states. They may cause cell and tissue damage by their chemical modification of proteins, carbohydrates, nucleotides, and lipids. Under physiological conditions OFRs are part of normal regulatory circuits and are neutralized by antioxidants. Infections are one cause of increased OFR production. The aims of our study were to assess whether the increased oxidative stress in experimental otitis media with effusion (OME) is reflected in erythrocytes by lipid peroxidation and to survey the alterations in oxidant and antioxidant enzyme activities in experimental OME in guinea pigs. Erythrocyte total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) activities, and malondialdehyde (MDA) level were measured in 6 guinea pigs with OME and in 6 controls. The TSSA, SOD, XO activities, and MDA level in experimental OME were significantly higher than in controls. No significant differences were found in erythrocyte NSSA and CAT activities. In experimental OME induced by histamine injection, increased OFR production was observed, suggesting that OFRs may play an important role in cell and tissue damage due to OME.