The bacteriologic response to antimicrobial therapy of 38 infants with neonatal meningitis was studied. Cerebrospinal fluid (CSF) cultures from 15 of 16 infants with meningitis due to gram positive organisms were sterilized promptly. Thirteen of 22 infants with meningitis due to gram negative pathogens had positive CSF cultures for 2 to 11 days (mean, 6.0 days) after initiation of therapy. The first sterile cultures of CSF from these infants were obtained from 1 to 18 days (mean, 8.2 days) after the start of therapy. The concentration of antibiotics and the in vitro bactericidal titers of 24 CSF specimens were determined. The antibiotic concentrations in CSF varied greatly and demonstrable bactericidal titers in vitro did not ensure sterility of the CSF cultures.