8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $mu extrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $mu extrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2eta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($pm$SD) $C_{max}$ after i.v. administration were 11.6$pm$1.6 $mu extrm{g}$/ml for 8-FCP, and 10.2$pm$1.3 $mu extrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$pm$1.8 $mu extrm{g}$/ml for 8-FCP and 1.1$pm$0.9 $mu extrm{g}$/ml for CP, respectively. The t$_{1/2eta}$ was 67.9$pm$8.4 min for 8-FCP, and 76.4$pm$7.2 min for CP. The F was 88.6$pm$6.3% for 8-FCP, and 40.7$pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.