Three commonly used antibiotic regimens for the prevention of enterococcal endocarditis were administered parenterally to six healthy men in a crossover manner. The regimens included 1 gm of streptomycin intramuscularly (IM) in combination with (1) procaine penicillin 600,000 units plus aqueous penicillin G 200,000 units IM; or (2) ampicillin 25 mg/kg intravenously (IV); or (3) ampicillin 1 gm IM. The combinations containing ampicillin IM or IV with streptomycin produced bactericidal activity at dilutions of 1:2 or greater for the majority of the strains, whereas the penicillin-streptomycin regimen did not. All regimens were poorly bactericidal against three strains of enterococci which were highly resistant to streptomycin. These data suggest that ampicillin plus streptomycin is the preferred regimen for prophylaxis.