Stenotrophomonas maltophilia is an important emerging pathogen causing a variety of infections in severely ill patients. This microorganism is inherently resistant to many antibiotics, and only a few therapeutic options are available. The principal aim of this study was to assess the in vitro activity of new quinolones against this pathogen. Three hundred and twenty-six single clinical isolates were tested in this study. The MIC(90) was 16 mg/L for ciprofloxacin, 8 mg/L for levofloxacin and gatifloxacin, 4 mg/L for trovafloxacin, moxifloxacin and sparfloxacin and 2 mg/L for clinafloxacin. At a 2 mg/L concentration, a C(max) lung:MIC ratio of >/=10 can be reached for 95%, 84.3%, 83.1% and 81.5% of isolates, respectively, for clinafloxacin, trovafloxacin, moxifloxacin and sparfloxacin (P < 0. 001 compared with levofloxacin and ciprofloxacin). In spite of the rare but serious adverse events associated with the new-generation quinolones, these agents may become very useful in the treatment of certain severe or life-threatening infectious conditions due to S. maltophilia, notably lower respiratory tract infections.