We tested the synergistic activity of imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK 0787) (20 μg/ml) or penicillin (20 μg/ml) in combination with increasing concentrations of either streptomycin (5, 10, and 20 μg/ml) against 13 strains of streptomycin-susceptible enterococci or gentamicin (1, 3, and 5 μg/ml) against 13 strains of streptomycin-susceptible enterococci and 7 strains of streptomycin-resistant enterococci. At 24 h, penicillin together with each increment in streptomycin concentration resulted in a significant increase (P < 0.001) in killing of streptomycin-susceptible enterococci compared with imipenem and the corresponding concentration of streptomycin. Similarly, at 24 h, the magnitude of killing of streptomycin-susceptible enterococci by a combination of penicillin plus each increment of gentamicin concentration was significantly greater (P < 0.001) than that of the combination of imipenem and the corresponding concentration of gentamicin. Against streptomycin-resistant enterococci, penicillin together with each increment of gentamicin concentration killed significantly more enterococci (P < 0.02) than did the combination of imipenem and the corresponding concentration of gentamicin. When combined with an aminoglycoside, the synergistic activity in vitro against enterococci of imipenem was significantly less than that of penicillin.