This study compares the in vitro activity of novel fluoroquinolones against clinical Legionella pneumophila isolates. We determined both the MICs and intracellular efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin in the Mono Mac 6 infection model. Six legionella strains were tested and all proved highly susceptible to the fluoroquinolones. Clinafloxacin and trovafloxacin were found to have the lowest MICs (0.004 mg/L) followed by levofloxacin and moxifloxacin (0.015-0.03 mg/L). In the Mono Mac 6 infection model, inhibition of L. pneumophila was achieved at concentrations four times below the respective in vitro MICs. Concentrations as low as 0.015 mg/L of moxifloxacin and levofloxacin, 0.004 mg/L of trovafloxacin and 0.002 mg/L of clinafloxacin markedly decreased viable intracellular bacterial counts. These data strongly support further clinical evaluation of new fluoroquinolones for empirical treatment of lower respiratory tract infection including atypical pneumonia caused by L. pneumophila.