The in-vitro activities of five fluoroquinolones were tested against 70 ciprofloxacin-resistant and 46 ciprofloxacin-susceptible unrelated isolates of Staphylococcus aureus. All 116 S. aureus isolates were studied for the presence of mutations in the grl and gyr loci. The order of efficacy of the fluoroquinolones tested, from least to most active, was: ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039), in response to all characterized mutations in grlA, grlB, gyrA and gyrB. Moxifloxacin was active against most S. aureus isolates tested (MIC90 = 1 mg/L for ciprofloxacin-resistant isolates) and was less influenced by known mutations.