Vancomycin monotherapy of deep-seated staphylococcal infection may be associated with poor bacteriological response. We evaluated 24 unique patient isolates of methicillin-resistant Staphylococcus aureus (MRSA) for vancomycin-gentamicin synergism by determining time-kill curves for vancomycin at 10 micrograms/ml and gentamicin at 1 microgram/ml. Nine MRSA strains showed high-level gentamicin resistance (HLGR) (MIC, > 500 micrograms/ml), and 15 did not. Vancomycin-gentamicin demonstrated synergism against none of the HLGR strains. For the non-HLGR strains, gentamicin agar dilution MICs ranged from 0.5 to > 128 micrograms/ml. Vancomycin-gentamicin demonstrated synergism against six of these strains and indifference against nine of them. There was no relationship between the agar dilution MIC of gentamicin and the occurrence of synergism against non-HLGR strains. We conclude that a gentamicin MIC of > 500 micrograms/ml predicts a lack of vancomycin-gentamicin synergism for strains of MRSA. For non-HLGR strains, synergism is not predictable from the gentamicin MIC.