Quinupristin-dalfopristin, a novel injectable streptogramin, was evaluated for both in vitro and in vivo antibacterial activities in comparison with those of erythromycin, azithromycin, clindamycin, vancomycin, ampicillin, imipenem, and ciprofloxacin. Quinupristin-dalfopristin had high activity against staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus (MRSA), and penicillin-resistant Streptococcus pneumoniae, with MICs at which 90% of strains tested are inhibited (MIC 90 ) equal to 1 μg/mL or less. Against Enterococcus spp, quinupristin-dalfopristin was less active than vancomycin with an MIC 90 of 32 μg/mL, while against Haemophilus influenzae, Moraxella (B) catarrhalis and Bordetella pertussis, the MIC 90 s of quinupristin-dalfopristin were 4.0, 1.0, and 0.1 μg/mL, respectively. The minimal bactericidal concentration (MBC) values of quinupristin-dalfopristin against methicillin-susceptible staphylococci, penicillin-resistant S. pneumoniae and H. influenzae were similar to the MIC values, while the MBCs for MRSA and E. faecalis were at least 8-fold greater than the corresponding MIC values. In a murine lung infection model using penicillin-resistant S. pneumoniae, treatment with quinupristin-dalfopristin resulted in a significant reduction in the number of organisms in the lungs compared with that in untreated animals or erythromycin-treated mice (P<0.05). The in vivo efficacy of quinupristin-dalfopristin against experimental septicemia caused by penicillin-sensitive S. pneumoniae and MRSA was less than that using vancomycin and imipenem-cilastatin, even though it had higher in vitro activity.