Cefotaxime and other cephalosporins were retrospectively evaluated for the treatment of meningitis and non-central nervous system (CNS) infections due to ampicillin-resistant Haemophilus influenzae type b (Hib). Between January 1985 and February 1989, 45 cases of meningitis and 27 cases of non-CNS infection due to ampicillin-resistant Hib were documented at Texas Children's Hospital in Houston. Of the 45 children with meningitis, 26 (57.8%) were treated with cefotaxime, 11 (24.4%) with chloramphenicol, and three (6.7%) with cefuroxime; five children (11.1%) were initially given chloramphenicol but later received cefotaxime instead. In addition, 14 chloramphenicol-treated patients from a previous study were included in this analysis. There were no significant differences in terms of neurologic sequelae or other complications (except diarrhea) between the cefotaxime and chloramphenicol groups. The efficacy of cefotaxime was equivalent to that of chloramphenicol for the treatment of ampicillin-resistant Hib meningitis. Cefuroxime was as safe and effective as chloramphenicol or cefotaxime for the treatment of non-CNS infections due to ampicillin-resistant Hib.