Various combinations of antistaphylococcal antimicrobial agents have been tested against 17 selected Staphylococcus isolates, including methicillin-susceptible and methicillin-resistant strains of S. aureus and coagulase-negative Staphylococcus species. With the checkerboard technique the following combinations were tested: oxacillin-ofloxacin, oxacillin-temafloxacin, oxacillin-fleroxacin, vancomycin-fleroxacin, gentamicin-fleroxacin, and rifampin-fleroxacin. Against methicillin-resistant staphylococci the combination oxacillin-quinolone tested at 35 degrees C always showed a fractional inhibitory concentration (FIC) index of less than 0.75, which is interpreted as synergistic or additive. Equal or more synergistic effects were observed at 30 degrees C. In contrast, when methicillin-susceptible Staphylococcus species were tested, the FIC for the combination oxacillin-quinolone was always 1 or 2, which is considered to be indifferent. For the other mentioned combinations the FICs were also 1 or 2. Killing kinetics showed synergistic or additive bactericidal activity for the combination oxacillin-ofloxacin against methicillin-resistant Staphylococcus species, killing 1.5 to 2.8 log10 CFU more of these per ml than did the most active drug after 24 h of incubation. This difference was not observed for methicillin-susceptible strains. In vitro evidence for the potential clinical use of quinolones in treating infections due to methicillin-resistant staphylococci in combination with a beta-lactamase-resistant penicillin is provided.