Free radical damage, as evidenced by lipoperoxidation, has previously been demonstrated to contribute to the inflammatory changes associated with acute otitis media. The present study was undertaken to evaluate whether lipoperoxidation continues to be present for a period of time after middle ear infection. Eighty-two 300- to 400-g guinea pigs were injected with Streptococcus pneumoniae in the left ear and sterile saline in the right ear as a control. Animals were examined and sacrificed on day 5, 10, 20, or 30; middle ear mucosa was harvested and assayed for lipid hydroperoxide content. A statistically significant increase in lipoperoxidation was seen at each time point studied, compared with controls. Lipoperoxidation was highest at days 5 and 10; a significant decrease was seen at days 20 and 30. Histologic sections of middle ear mucosa of two animals per group were prepared and evaluated for inflammation. These results demonstrate that lipoperoxidation may contribute to middle ear inflammation for a significant period of time after acute infection; the findings are discussed in light of other work on the role of free radicals in otitis media.