Recently, we reported that ciprofloxacin, an antimicrobial agent with โฅ-aminobutyric acid (GABA A ) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague-Dawley rats (n โซุโฌ 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 mol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4-day period. An additional 45 rats (n โซุโฌ 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 mol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3 H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P F .05). Survival figures in the norfloxacin-and putrescinetreated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the D-gal ุ saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal ุ ciprofloxacin and D-gal ุ putrescine groups (10.2 ุ 3.3 vs. 18.2 ุ 5.1 and 18.8 ุ 6.8 ุ 10 3 dpm/mg DNA respectively; P F .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 ุ 3.7; ciprofloxacin, 47.4 ุ Abbreviations: FHF, fulminant hepatic failure; GABA, โฅ-aminobutyric acid; D-gal, D-galactosamine; ALT, alanine transaminase; PCNA, proliferating cell nuclear antigen.