The in vitro activity of clinafloxacin (formerly CI-960, AM-1091, PD-127391) was compared with other fluoroquinolones, cephalosporins, gentamicin, vancomycin, imipenem, piperacillin/tazobactam, clindamycin, and metronidazole against 2000 recent clinical strains from a large number of hospitals in the United States. Overall, clinafloxacin was the most active compound tested. Against Pseudomonas aeruginosa, clinafloxacin and ciprofloxacin demonstrated comparable activity (88% and 80% susceptible, respectively), and were four- to 16-fold more potent than levofloxacin (MIC90, 16 micrograms/ml) or trovafloxacin (MIC90, 32 micrograms/ml). Among anaerobic bacteria, clinafloxacin (MIC50s, 0.25-0.5 microgram/ml) and trovafloxacin (MIC50s, 0.5-2.0 micrograms/ml) were the most active quinolones, whereas metronidazole, imipenem and piperacillin/tazobactam were the most potent comparators. Clinafloxacin demonstrated sustained activity when compared to several available peer drugs against contemporary clinical isolates. The clinafloxacin spectrum against the 15 important pathogens monitored ranged from nil or 4.0% (vancomycin-resistant enterococci) to 100.0% (four different species) susceptible with an average percent susceptibility of 94.0%. This degree of potency and spectrum for clinafloxacin provides a wide potential for use against many species with established resistance to other anti-microbial classes.