Francisella tularensis is a potent pathogen and a possible bioterrorism agent, for which quinolones offer promising new therapeutic options. There are, however, no data on the susceptibility to quinolones of natural isolates of F. tularensis tularensis, the highly virulent North American subspecies. In the present study, 8 isolates of F. tularensis tularensis, originating from 8 different states of the USA, and 16 US isolates of F. tularensis holarctica were tested. All 24 isolates showed MIC values < or = 0.125 mg/l to 6 different quinolones. Against ciprofloxacin, the predominant quinolone used to date in therapy against subspecies holarctica, MIC values were consistently < or = 0.064 mg/l. Thus quinolones seem to be promising options for the treatment of tularemia, including cases caused by the highly virulent subspecies F. tularensis tularensis.