The in vitro activity of fosfomycin alone and in combination with rifampin, pefloxacin and imipenem was studied by the time-kill method against staphylococci. Fosfomycin, pefloxacin and imipenem used at concentrations within the therapeutic range, exerted a bactericidal effect, whereas rifampin acted as a bacteriostatic drug. The combination of fosfomycin and rifampin was found to be antagonistic against rifampin-susceptible strains and indifferent for rifampin-resistant isolates. Fosfomycin combined with pefloxacin usually produced an indifferent effect. The interaction between fosfomycin and imipenem was mainly indifferent but synergism occurred with methicillin-resistant strains and antagonism was observed for one methicillin-susceptible isolate of Staphylococcus aureus.