To our knowledge, we report the first failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae (MICs of penicillin and cefotaxime, 1 µg/mL). Cure was achieved with a 14-day course of intravenous and intrathecal vancomycin. We recommend that in cases of meningitis caused by strains of S. pneumoniae for which MICs are ⩾ 1 µg/mL, cefotaxime should be used with caution; however, if therapeutic failure is suspected therapy should be changed to intravenous and intrathecal vancomycin.