Rapid bactericidal effect is essential for therapy of severe Staphylococcus aureus infections in children. The in vitro activity of clinically achievable levels of vancomycin and its combinations with gentamicin, amikacin and rifampin plus amikacin was studied with the time-kill curve method at 2.5, 4, 6, 24 and 48 hours against 20 strains of Staphylococcus aureus isolated from children with severe staphylococcal infection. Vancomycin alone exerted a bactericidal effect at 48 hours. However, with the combinations vancomycin plus gentamicin, vancomycin plus amikacin and vancomycin plus amikacin plus rifampin a bactericidal effect was respectively observed at 24, 6 and 4 hours. Most rapid killing was achieved with vancomycin plus rifampin plus amikacin. Thus this antibiotic combination seems the most appropriate for initial treatment of severe staphylococcal infections in children.