The purpose of this study was to develop a model of bacterial meningitis in young adult rats for assessing the efficacy of antimicrobial agents. Sixty 200- to 300-g male Sprague Dawley CD rats were inoculated intracisternally with 5.78 log10 CFU of a clinical isolate of Streptococcus pneumoniae in 5% hog gastric mucin. Inoculated rats were assigned to six groups containing 10 animals each. Group-1 rats served as controls and did not receive antibiotics. Rats of groups 2 to 4 received (subcutaneously every 12 h) cefotaxime (25, 6.25, and 1.56 mg/kg of body weight respectively). Rats of groups 5 and 6 received ampicillin (50 and 12.5 mg/kg respectively) and gentamicin (2.0 and 0.5 mg/kg respectively). Five additional Sprague Dawley CD rats were inoculated with only gastric hog mucin and were assigned to group 7. At postinoculation day 4 all animals were euthanized. Cerebral spinal fluid was collected for culturing. Brains were harvested for histologic examination and culturing. Untreated, infected control (group-1) animals were culture-positive for S. pneumoniae in the brain and cerebral spinal fluid. Of the antibiotic regimens evaluated, only cefotaxime (25 mg/kg) eradicated bacteria from the cerebral spinal fluid and brain. Cefotaxime at 25 or 6.25 mg/kg significantly (P < or = 0.05) decreased the bacterial burden of S. pneumoniae, whereas cefotaxime at 1.56 mg/kg and ampicillin/gentamicin combinations did not. There was histopathological evidence of subacute meningitis in infected rats. No meningitis was observed in rats receiving 25 mg of cefotaxime/kg. This model demonstrates the ability to induce bacterial meningitis with S. pneumoniae in adult rats and the ability to clear infection in 90 to 100% of the animals by administration of cefotaxime at dosages of 6.25 and 25 mg/kg given subcutaneously every 12 h.