The activity of quinupristin/dalfopristin was compared with that of other widely used antibiotics against 355 strains isolated from patients with endocarditis. MICs were determined by a standard agar dilution method. Quinupristin/dalfopristin was inhibitory at 1 mg/L for all coagulase-negative staphylococci (n = 36) and for the majority of Staphylococcus aureus strains (n = 87). The activity of quinupristin/dalfopristin against 186 viridans streptococci was somewhat dependent on the species, with MIC50s ranging from 0.5 to 2 mg/L, being least active against Streptococcus bovis and most active against Streptococcus gordonii and Streptococcus mitis. For the staphylococci, quinupristin/dalfopristin was as active against erythromycin-susceptible as erythromycin-resistant strains. Viridans streptococci showed a slight but significant correlation between sensitivity to erythromycin and quinupristin/dalfopristin. It is concluded that quinupristin/dalfopristin has the potential to treat serious infections such as endocarditis caused by Gram-positive cocci.