First of all, vancomycin (VCM) showed good antimicrobial activity against Staphylococcus aureus including methicillin-sensitive and -resistant strains. MIC90 of VCM was 1.56 micrograms/ml. Effects of different 2-drug combinations among cefamandole (CMD), flomoxef (FMOX) and imipenem (IPM), and activity of VCM alone were examined in vitro against 5 clinical isolates of methicillin-sensitive S. aureus (MSSA) and 22 isolates of methicillin-resistant S. aureus (MRSA). In a checkerboard study, synergism was observed against 4 strains of the 5 MSSA and all 22 strains of the MRSA with IPM and CMD, FMOX and IPM, and FMOX and CMD combinations. Mean MICs of these combinations were as low as one-fourth to one-tenth as those of individual drugs.