Pharmacokinetic differences between ampicillin and carbenicillin in the cerebrospinal fluid (CSF) were evaluated in experimental staphylococcal meningitis in rabbits after a single intravenous administration of 100 mg/kg dose of each drug. Half-lives (T 1/2) in CSF and CSF/serum ratios of T 1/2 were 52 minutes and 2.1 for ampicillin and 23 minutes and 1.3 for carbenicillin, respectively. These findings indicate that ampicillin is eliminated from CSF more slowly than carbenicillin. Penetration rates were calculated from CSF/serum ratios of area under the curve (AUC) and were 16.8% for ampicillin and 11.6% for carbenicillin, although the maximum concentration (Cmax) of carbenicillin in CSF was twice as high as that of ampicillin. Thus the penetration rate appeared to be influenced more by T 1/2 in CSF than by Cmax. Cmax in CSF was obtained at 15 minutes for carbenicillin and 30 minutes for ampicillin. As to carbenicillin there were considerable individual variations in CSF levels. The above observations suggest that T 1/2 and AUC in CSF are important parameters when evaluating the usefulness of an antibiotic in the treatment of bacterial meningitis.