The intracellular bactericidal activity of fosfomycin was compared to that of other anti-staphylococcal agents. Two staphylococcal strains (one isolate of Staphylococcus aureus and one isolate of Staphylococcus epidermidis) were incubated in vitro with human granulocytes isolated from volunteers. After phagocytosis and removal of residual extracellular bacteria, the cells were resuspended in the presence of clinically relevant concentrations of fosfomycin, teicoplanin, vancomycin and rifampin. The number of bacteria surviving intracellularly was determined by colony counts after osmotic lysis of the granulocytes at different time intervals. Incubation with fosfomycin resulted in a mean reduction of intracellular bacteria by approximately two logs of ten within 18 h for both staphylococcal strains. Although less effective than rifampin, fosfomycin showed a significantly higher intracellular activity than the glycopeptide antibiotics in this model.