The aim of this study was to evaluate the antibacterial activity of older (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory concentrations (MICs) were determined, according to the NCCLS guidelines, against the following respiratory tract pathogens: penicillin-susceptible and -resistant Streptococcus pneumoniae, beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae and beta-lactamase-positive Moraxella catarrhalis. In addition, we evaluated the minimal bactericidal concentrations of the same antibiotics against all the pneumococci and the haemophili. Finally, the activity of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci were investigated by time-kill analysis. All fluoroquinolones tested exhibited a similar, good activity against H. influenzae and M. catarrhalis. Against S. pneumoniae, irrespective of penicillin susceptibility, moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of all strains was obtained after 24 h with moxifloxacin at 2 x MIC, whereas other antimicrobials obtained similar results at 4 x MIC. Moxifloxacin is characterized by an improved activity against respiratory pathogens, including penicillin-resistant and -susceptible S. pneumoniae. Its activity is not influenced by beta-lactamase production. These results suggest that moxifloxacin represents a promising alternative for treatment of respiratory tract infections.