To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.