We treated nine patients (10 episodes) with meningitis caused by Streptococcus pneumoniae isolates with decreased susceptibilities to broad-spectrum cephalosporins with high doses of cefotaxime (300 mg/kg of body weight per day; maximum dose, 24 g/day). Early adjunctive therapy with dexamethasone was also administered. Cefotaxime MICs were 0.5 (three episodes), 1 (five episodes), and 2 (two episodes) micrograms/ml, and MBCs ranged from 1 to 4 micrograms/ml. Therapy was well tolerated, and all patients experienced prompt clinical improvement. One patient died 8 days after the end of therapy, the central nervous system infection had already been cured, and the remaining patients recovered without relapses.