The efficacy of ciprofloxacin for experimental aortic valve endocarditis in rabbits infected by either a methicillin-susceptible or a methicillin-resistant strain of Staphylococcus aureus was compared with standard therapy of nafcillin or vancomycin, respectively. After 4 days of therapy, ciprofloxacin reduced the counts of organisms in aortic valve vegetations as effectively as the standard regimen for both susceptible and resistant strains. Mean concentrations of ciprofloxacin in serum achieved 1 h after a dose exceeded the MBC for each strain by twofold or less. In these experiments ciprofloxacin was as efficacious as standard regimens currently used to treat staphylococcal infections in humans.