The synergistic activity of levofloxacin and oxacillin against levofloxacin-resistant isolates of methicillin-resistant Staphylococcus aureus was tested by the time-kill method. The combination of levofloxacin at 1/4 the MIC for the isolate plus oxacillin at 8 micrograms/ml (< 1/4 the MIC) was synergistic against seven of nine isolates at 8 h, although no significant synergy was demonstrated at 24 h. This combination may prove to be effective against multidrug-resistant methicillin-resistant S. aureus, and further studies are warranted.