We tested the in vitro inhibitory and bactericidal activity of minocycline against 26 methicillin-susceptible Staphylococcus aureus, 24 methicillin-resistant S. aureus, 1 methicillin-susceptible coagulase-negative staphylococci, and 33 methicillin-resistant coagulase-negative staphylococci. Minocycline and rifampin had MIC90 results in the susceptible range, but MBCs were markedly elevated for minocycline alone (MBC50 greater than 32 micrograms/ml). The combination of minocycline and rifampin was synergistic for 30% of the isolates with the highest rates of synergy being against methicillin-resistant isolates.