The in vitro activities of the newer agents Deptomycin, Difloxacin, A-56620 and Ciprofloxacin were compared with those of vancomycin, rifampin and gentamicin against methicillin-susceptible and -resistant Staphylococcus aureus and coagulase-negative staphylococci. All isolates were susceptible to vancomycin, rifampin, deptomycin and the quinolones tested. Newer agents had activity superior to that of vancomycin, whereas the activity of the newer agents and rifampin was comparable. Gentamicin resistance was frequent, however, the resistant staphylococci were susceptible to other antibiotics tested.