Excellent clinical results were observed with the combination therapy of chloramphenicol with beta-lactam-antibiotics in the treatment of purulent meningitis. This came as a surprise as bacteriostatic antibiotics like chloramphenicol are commonly thought to antagonize the bactericidal action of penicillin or ampicillin. We reevaluated the mode of action of chloramphenicol against the three most common meningeal pathogens after the newborn period. Chloramphenicol was found to be bactericidal against H. influenzae, Streptococcus pneumoniae and Neisseria meningitidis at clinically achievable levels in the CSF. In addition chloramphenicol showed synergistic action with ampicillin against H. influenzae which can possess clinical relevance particularly with the high inoculum of 10(7) organisms/ml which is frequently seen in bacterial meningitis. No synergism was found against Pneumococci and Meningococci but also no antagonism of the lower MIC and MBC values seen with ampicillin and penicillin G. The combination of chloramphenicol with either penicillin or ampicillin constitutes a clinically successful therapeutic regimen which is now also proven by in vitro investigations.