The in-vitro activities of four new fluoroquinolones, E-4749, E-4874, E-4884 and E-4904, were compared with that of ciprofloxacin and sparfloxacin against 1106 clinical isolates. Against majority of Enterobacteriaceae, general antibacterial activities of E-4749 (MIC90s 0.06-1 mg/L), E-4874 (MIC90s, 0.03-0.25 mg/L) and E-4884 (MIC90s 0.01-0.5 mg/L) were comparable or slightly lower than those of ciproloxacin (MIC90s 0.01-0.25 mg/L) and sparfloxacin (MIC90s 0.01-1 mg/L). The activity of E-4904 (MIC90s 0.06-2 mg/L) was lower than those of its analogues. Most of the Escherichia coli which were resistant to ciprofloxacin (MIC > or = 2 mg/L) and Serratia spp., were resistant to the new fluoroquinolones. beta-Lactamase producing strains of Moraxella catarrhalis were very susceptible to these compounds (MICs < or = 0.008 mg/L). Most of Pseudomonas aeruginosa, non-aeruginosa Pseudomonas spp., Xanthomonas maltophilia, and Acinetobacter spp. were resistant to the new quinolones (MIC90s 8- > 16 mg/L). On the contrary, these new antimicrobials were active against the majority of the Aeromonas spp. (MIC90s < or = 0.5 mg/L). E-4749, E-4874, E-4884 and E-4904 remained active (MIC90s < or = 0.25 mg/L) against Staphylococcus aureus strains susceptible to methicillin. However, its activity was two- to eight-fold lower than that of ciprofloxacin (MIC90 0.03 mg/L) and sparfloxacin (MIC90 0.06 mg/L). Against S. aureus resistant to methicillin or ciprofloxacin, activity of these new compounds and comparators agents, was very low (MIC90s 2- > 16 mg/L). Most of the strains of Enterococcus faecalis were resistant (MIC90s > 16 mg/L). The activity of E-4874, E-4904 and sparfloxacin (MIC90 1 mg/L for each one) was higher than that of the rest of the agents tested. E-4874 (MIC90 0.25 mg/L) was four-fold more active than the other antibacterials tested (MIC90 2 mg/L) against Listeria monocytogenes. No new quinolone was active against Bacteroides fragilis (MIC90s 4-16 mg/L), Bacteroides thetaiotaomicron (MIC90s 8- > 16 mg/L), and other B. fragilis group (MIC90s 16- > 16 mg/L). Ciprofloxacin (MIC90s > 16 mg/L), and sparfloxacin (MIC90s 8-16 mg/L) also were inactive. E-4874 (MIC90 4 mg/L) was the most active quinolone tested against B.fragilis.