Methicillin-resistant Staphylococcus aureus (MRSA) presently represents approximately 30% of clinical isolates of S. aureus in the USA. Many strains are additionally resistant to erythromycin, 15- and 16-membered macrolides (e.g. azithromycin, spiramycin), clindamycin, aminoglycosides and/or quinolones. A review of the literature shows that quinupristin/dalfopristin, a semisynthetic derivative of pristinamycin, exhibits good in-vitro activity against methicillin-sensitive S. aureus and MRSA (mean MIC90 0.25-1.0 and 0.5-2.0 mg/L, respectively). Its in-vitro bacteriostatic activity is also unaffected by resistance phenotypes for erythromycin, ciprofloxacin, rifampicin or gentamicin. Among erythromycin-resistant MRSA strains, those with constitutive (macrolide and lincosamide) resistance are only 2-fold less sensitive as strains with inducible (14- and 15-membered macrolide only) resistance (MICs 0.5-1.0 and 0.25-1.0 mg/L, respectively). Quinupristin/dalfopristin is at least as active as vancomycin and more active than ciprofloxacin and erythromycin against MRSA. It generally has a more rapid bactericidal action than vancomycin and oxacillin against many strains of MRSA. The bactericidal activity of quinupristin/dalfopristin may be affected by macrolide resistance phenotype: S. aureus strains susceptible or inducibly resistant to macrolides are killed within 6 h, whereas a number of strains constitutively resistant to macrolides remain viable after 12 h. The clinical significance of this laboratory phenomenon requires investigation, possibly in additional animal models of infection.