Sparfloxacin, a new difluorinated quinolone antibiotic, was employed in the treatment of catheter-induced endocarditis in rabbits infected with a methicillin-resistant strain of Staphylococcus aureus (MRSA). Animals (n = 12) in the study group received sparfloxacin, 25 mg/kg body weight every 12 h intravenously. Comparison groups were untreated controls (n = 9) and animals injected with vancomycin (n = 13) at the same dosage. MICs and MBCs of the test organism were both 1.56 mg/l for vancomycin and 0.15/0.30 mg/l for sparfloxacin. Antibiotic treatments started 24 h after bacterial challenge and lasted 4 days until sacrifice. In comparison with no treatment, both sparfloxacin and vancomycin significantly reduced the bacterial counts in aortic vegetations, while no significant difference was found between the two antibiotics. Combination of the two antibiotics, tried in a smaller group of rabbits (n = 3) showed no advantages over either single-drug therapy. Our results suggest that sparfloxacin is a potentially useful agent, at least in the rabbit model, for treating MRSA endocardial infections.