Three cases of persistence or relapse of infection in Hemophilus influenzae type b meningitis treated with ampicillin sodium are presented. Factors that may have contributed to bacteriological failure were infection of the subdural space, the use of the intramuscular route of administration, the presence of ventriculitis and hydrocephalus, and the development of a brain abscess due to H influenzae. Eight previously reported cases of ampicillin failure were also reviewed to determine possible reasons for failure. These included inadequate dosage, intramuscular administration, and sequestration of organisms in inaccessible sites. On the basis of available information it is recommended that ampicillin should remain the drug of choice for the treatment of H influenzae meningitis since there is little reason to believe that reinstating chloramphenicol as the preferred drug would produce better results.