The activity of moxifloxacin, a novel 8-methoxyquinolone, was evaluated against 1,218 respiratory pathogens isolated in nine Spanish hospitals and was compared with ciprofloxacin, sparfloxacin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime, erythromycin and clarithromycin. Moxifloxacin exhibited an excellent in vitro activity against most tested isolates with MIC90 values of 0.25 mg/l for Streptococcus pneumoniae and viridans group streptococci; 0.12 mg/l for Streptococcus pyogenes; 0.25 mg/l for Streptococcus agalactiae; 0.06 and 4 mg/l for methicillin-susceptible and -resistant Staphylococcus aureus, respectively; 0.06 mg/l for Haemophilus influenzae and 0.12 mg/l for Moraxella catarrhalis. Moxifloxacin susceptibility rates were not affected by penicillin resistance in S. pneumoniae and S. viridans, by the betalactamase production in H. influenzae and M. catarrhalis or by macrolide resistance. Moxifloxacin was twice as active as sparfloxacin and four to sixteen times more active than ciprofloxacin against Gram-positive isolates. Sparfloxacin and ciprofloxacin were slightly more active than moxifloxacin when tested against H. influenzae and M. catarrhalis isolates. The microbiological data obtained confirm that moxifloxacin is a promising antimicrobial agent for treating respiratory tract infections.