The purpose of this study was to identify mediators of brain oedema formation in experimental pneumococcal meningitis. In a rat model of pneumococcal meningitis brain water content was significantly elevated 6 hours post infection (79.69% +/- 0.24 compared to 78.94% +/- 0.16 in the control group, mean +/- SEM, p less than 0.05). Brain oedema formation was completely blocked by superoxide dismutase (132,000 U/kg i.v. per 6 hours: n = 6), pretreatment with dexamethasone (3 mg/kg i.p., n = 3), or administration of dexamethasone at two hours after pneumococcal injection (n = 5). Pretreatment with indomethacin (10 mg/kg i.v., n = 5) attenuated the brain oedema formation. These findings suggest that oxygen derived free radicals act as mediators of brain oedema formation during the early phase of experimental bacterial meningitis. Cyclooxygenase metabolites may provide one possible source for the generation of oxygen derived free radicals in bacterial meningitis.