The effectiveness and safety of ceftriaxone and cefotaxime in the short-term treatment of primary bacterial meningitis were compared using a prospective, randomized, multicenter study design. Children between the ages of 6 weeks and 16 years received either ceftriaxone as a single dose (100 mg/kg on the first day followed by 75 mg/kg/day) or cefotaxime as four divided doses (200 mg/kg/day) for 4-7 days. A total of 82 patients (44 ceftriaxone, 38 cefotaxime) with documented bacteria in the CSF were studied. In patients receiving ceftriaxone, full recovery occurred in 79.5% while a further 13.7% recovered with neurologic sequelae. Full recovery was observed in 71.1% of children treated with cefotaxime with sequelae in a further 23.6% (no statistically significant differences between drugs). The time to clinical improvement and resolution of fever (3-4 days) was also similar for both drugs. All but 1 of the 82 patients studied had negative CSF cultures within 24 h of the beginning of therapy consistent with the excellent penetration into the CSF (trough concentrations of 2.7 mg/l for both drugs at the end of therapy). No differences were observed in the incidence of clinically significant adverse events. Ceftriaxone and cefotaxime are both effective in the treatment of bacterial meningitis. Ceftriaxone offers an advantage in case of administration since it is administered as a single daily dose.