Three consecutive doses of 75 mg of cefoxitin per kg were given intravenously every 6 h (225 mg/kg), in addition to penicillin or ampicillin, to 24 patients on days 4 and 5 and 9 and 10 of therapy for meningitis. Haemophilus influenzae b was isolated from cerebrospinal fluid (CSF) of 21 patients, Streptococcus pneumoniae from 2 patients, and Neisseria meningitidis from 1 patient. The median minimal inhibitory and bactericidal concentrations of cefoxitin for 16 isolates of H. influenzae b were 0.312 and 0.625 micrograms/ml, respectively. Sixteen of 18 isolates of H. influenzae b and S. pneumoniae were killed by 2.5 micrograms of cefoxitin per ml. Mean levels in CSF peaked at 1 h at 6 and 4.9 micrograms/ml on days 5 and 10, respectively. CSF levels on days 5 and 10 were greater than or equal to twice the median minimal inhibitory and bactericidal concentration in 20 and 18 patients, respectively. However, bacterial levels in CSF were greater than or equal to 2.5 micrograms/ml in only 11 of 23 patients on days 5 and 10. No significant adverse effects were found. These data indicate that at this dosage, cefoxitin may not reach levels in the CSF required for killing all susceptible strains of H. influenzae b and S. pneumoniae.