A randomized therapeutic trial of carbenicillin (CB) or ampicillin (AMP) in purulent meningitis was performed in 86 pediatric and adult patients (41 Haemophilus influenzae, 22 Streptococcus pneumoniae, 13 Neisseria meningitidis, and 10 of unknown etiology). All isolates, incuding H. influenzae, were susceptible to CB and AMP. Median cerebrospinal fluid (CSF) antibiotic concentrations were 0.85 and 1.60 μg/ml for CB and AMP, respectively, during administration of daily doses of 400 mg/kg and 0.65 and 0.45 μg/ml, respectively, on daily doses of 200 mg/kg. Higher CSF concentrations, up to a median concentration of 4.5 μg/ml, were observed in patients with CSF protein concentrations ≥75 mg/100 ml. Clinical responses were equivalent on either antibiotic regimen. Among AMP patients (45), 8 had significant residua and 3 died; among CB patients (41), 5 had residua and none died. However, 38% of H. influenzae patients treated with CB had positive CSF cultures on day 1 follow-up lumbar punctures, compared with only 5.8% of AMP patients with H. influenzae. The significance of a delay of CSF sterilization among CB-treated patients is unknown, since there was no correlation between persistence of hemophilus organisms and the frequency of adverse outcome. AMP and CB are equivalent for the treatment of bacterial meningitis due to susceptible organisms.