The in vitro activities of A56619 (difloxacin) and A-56620, two newer quinolones, have been compared with the activities of ciprofloxacin, ofloxacin, ceftazidime and netilmicin. A total of 782 clinical, bacterial isolates were employed. Minimal inhibitory concentrations (MICs) were determined under standard conditions with all isolates and, for 100 isolates against difloxacin and A-56620, with variation of agar pH and bacterial inoculum size. On a weight-for-weight basis, ciprofloxacin and A-56620 were the most active agents against Enterobacteriaceae (MIC90 = 0.03 and 0.12 mg/l, respectively). Difloxacin was the least active quinolone, particularly against Proteus, Morga-nella and Providencia spp. Except for ceftazidime, all agents were highly active against staphylococci, but difloxacin and ofloxacin were somewhat less active against Staphylococcus saprophytics. The streptococcal isolates were moderately sensitive to the quinolones, difloxacin being least active. Haemophilus influenzae and Neisseria gonorrhoeae were extremely susceptible to all the quinolones; nearly all isolates were inhibited by the lowest concentrations of the agents that were employed in the study (0.03 mg/l). The quinolones all showed moderate activity against Bacteroides fragilis. The activities of difloxacin and A-56620 were affected little by inoculum size. Difloxacin showed lower activity against most isolates at pH 8.0 as compared to the activity at pH 7.4 and 6.8. A-56620 was minimally influenced by pH variation.