In vitro activities of fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin were evaluated against 25,129 fresh bacterial isolates from 51 US hospital or medical center laboratories, beginning in October of 1990. Susceptibility rates were > or = 85% against most species of Gram-negative bacteria. Notable exceptions were Pseudomonas, Acinetobacter, Xanthomonas, and Providencia. The study drugs displayed similar activity against most Gram-negative species. At least 90% of oxacillin-susceptible staphylococci were susceptible but, of oxacillin-resistant strains, only approximately 60% of Staphylococcus epidermidis and 25% of Staphylococcus aureus were susceptible to the quinolones tested. Staphylococcus saprophyticus strains were less susceptible to fleroxacin (42%) than to the other compounds (79%-97%). Ofloxacin and ciprofloxacin were more active against streptococci, and none of the compounds demonstrated appreciable activity against enterococci. Thus, the spectra of activity of fluoroquinolones illustrate that they remain effective agents for the treatment of many types of infections caused by Gram-negative pathogens.