In vitro bactericidal experiments were performed with combinations of recombinant lysostaphin and various antibiotics against five strains of Staphylococcus aureus, including clinical isolates of methicillin-resistant S. aureus (MRSA). Sublethal concentrations of lysostaphin combined with beta-lactam antibiotics (including benzylpenicillin, methicillin, and cephalosporin B), bacitracin, or polymyxin B, exhibited rapid synergistic bactericidal activity against all S. aureus strains tested. Lysostaphin activity was additive when combined with either vancomycin, gentamicin, tetracycline, or erythromycin. Synergistic combinations of recombinant lysostaphin and antibiotics might be applicable to controlling cutaneous staphylococcal infections and MRSA carriage.