The bactericidal rate of nafcillin and the combination of nafcillin and gentamicin against Staphylococcus aureus were compared in vitro and in experimental endocarditis. The combination proved synergistic against 8 strains of S. aureus in broth. In rabbits with S. aureus endocarditis, the organism was eradicated more rapidly from cardiac vegetations when animals were treated with the combination than with nafcillin alone. Gentamicin alone was ineffective. This combination is under study in the therapy of acute endocarditis caused by penicillinase-producing S. aureus.