The efficacy of ciprofloxacin in treatment and prophylaxis of Staphylococcus aureus endocarditis in rats infected with a strain tolerant to the standard anti-staphylococcal antibiotics cloxacillin, vancomycin and teicoplanin was compared with its non-tolerant variant. After 5 days of treatment with ciprofloxacin 30 mg/kg subcutaneously every 8 h bacterial densities in vegetations from animals infected with the tolerant and the non-tolerant strain were similar. Resistance to ciprofloxacin did not emerge in either strain of S. aureus during treatment. In prophylaxis experiments a single dose of ciprofloxacin (30 mg/kg) administered 30 min before bacterial challenge afforded almost full protection for both the tolerant and the non-tolerant strain. At a lower dose of 6 mg/kg the protective effect was less compared with the higher dose, but no difference in the proportion of sterile vegetations was found between the two strains. Thus tolerance influenced neither treatment nor prophylaxis with ciprofloxacin. For strains of S. aureus tolerant to the usual anti-staphylococcal antibiotics ciprofloxacin could be a useful alternative for the treatment of infections.