In vitro antibacterial activity of imipenem-fosfomycin (IMP-FOS) combinations were studied against 31 clinical isolates of Staphylococcus strains: methicillin susceptible S. aureus (MSSA, 11 strains), methicillin resistant S. aureus (MRSA, 11 strains), methicillin resistant S. epidermidis (MRSE, 9 strains). The study was carried out by means of a microtiter checkerboard method (FICs and FBCs index) and killing-curves (3 strains). Imipenem antibacterial activity was good against MSSA (mean MICs of 0.12 micrograms/ml) but reduced against MRSA (16 micrograms/ml). Fosfomycin was regularly effective (CMI less than or equal to 64 micrograms/ml) against most strains. IMP-FOS combination was strongly synergistic (FIC less than 0.125) against MSSA and still synergistic with achievable therapeutic concentrations against heterogeneous MRSA and MRSE strains (mean FIC of 0.125, MIC in the combination of 1 microgram/ml). The bactericidal activity (FBCs and killing-curves) was limited against homogeneous MRSA and MRSE needing higher concentrations (8 micrograms/ml in the combination). In the 3 cases fosfomycin concentrations in combination remained low (1 to 2 micrograms/ml).