Three children had staphylococcal infections of the CNS. In two cases the organisms were resistant to methicillin sodium. Each case was treated with a combination of vancomycin hydrochloride and rifampin; in one instance vancomycin alone had been unsuccessful. The addition of rifampin resulted in prompt clinical and bacteriologic resolution. Satisfactory levels of rifampin were achieved by administering the drug either orally or intravenously, and in one patient oral administration of rifampin produced assayed levels in subdural pus many times that required for minimal bactericidal activity. Combination therapy with vancomycin and rifampin is recommended for staphylococcal infections of the CNS.