ABSTRACT: The activity of eight antimicrobial agents which might be used in the treatment of staphylococcal osteomyelitis was tested under anaerobic conditions similar to those found in chronically infected bone. An agar-dilution method was employed to determine the minimum inhibitory concentrations of tobramycin, vancomycin, teicoplanin, ciprofloxacin, clindamycin, ceftriaxone, ticarcillinclavulanic acid, and amoxicillin-clavulanic acid against 25 coagulase-positive and 25 coagulase-negative staphylococcal strains. The activity of tobramycin against coagulasepositive staphylococci, and of amoxicillinclavulanic acid and ticarcillin-clavulanic acid against coagulase-negative staphylococci was markedly decreased with anaerobiosis. Vancomycin, teicoplanin, and ciprofloxacin were active against coagulase-positive and coagulase-negative staphylococci under both aerobic and anaerobic conditions. It was also found that antibiotic concentrations comparable to the high levels which might be achieved with local antibiotic therapy of osteomyelitis were not sufficient to overcome the level of resistance (10µg/ml) of staphylococci which were not susceptible to tobramycin, clindamycin, ceftriaxone, and ticarcillin-clavulanic acid.