Eighty-one patients ages one month to 14 years with meningitis were randomized to receive either sulbactam (50 mg/kg per day) and ampicillin (400 mg/kg per day; 41 patients) or chloramphenicol and ampicillin (40 patients). The groups were comparable in terms of sex and degree of illness; however, more patients treated with chloramphenicol/ampicillin than patients treated with sulbactam/ampicillin were younger than 12 months of age (78% vs. 56%). Pathogens were isolated from the cerebrospinal fluid (CSF) of 65 (80%) of the 81 patients. In the sulbactam/ampicillin group, there were 18 Haemophilus influenzae isolates (one resistant to ampicillin), five Streptococcus pneumoniae, five Neisseria meningitidis, one Klebsiella pneumoniae, one Pseudomonas aeruginosa, and one Listeria. In the chloramphenicol/ampicillin group, there were 19 H. influenzae isolates, 10 S. pneumoniae, three N. meningitidis, one Haemophilus parainfluenzae, and one Citrobacter. Of 63 patients with assessable CSF pathogens, one (3%) of 29 treated with sulbactam/ampicillin died (S. pneumoniae) and six (18%) of 34 treated with chloramphenicol/ampicillin died (two, H. influenzae; three, S. pneumoniae; and one, Citrobacter). Twelve percent in the sulbactam/ampicillin group and 18% in the chloramphenicol/ampicillin group had neurologic sequelae. No clinically significant reactions or toxicities were noted. Sulbactam/ampicillin was as effective as chloramphenicol/ampicillin in the treatment of meningitis.