The disposition of enrofloxacin in sheep was investigated after single-dose intravenous administration of 2.5 mg/kg body weight. Blood samples were drawn from the jugular vein at predetermined times after drug administration. Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin were simultaneously determined by reverse-phase high performance liquid chromatography. The data collected were subjected to non-compartmental and compartmental kinetic analysis. Statistical model theory was used to determine non-compartmental pharmacokinetic parameters. Disposition of enrofloxacin was described by a three-compartment open model with elimination from the central compartment following intravascular administration. The elimination half-life, the volume of distribution, and the area under the concentration vs time curve (AUC) were 4.31 h, 1.10 l/kg and 9.24 µg·h/ml, respectively. Enrofloxacin was metabolised to ciprofloxacin and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.26 after intravenous administration. With predictive models of efficacy (maximum plasma concentrations/minimum inhibitory concentrations [Cmax/MIC] and AUC/MIC ratios in plasma) for most of the sheep pathogen microorganisms, enrofloxacin produced scores higher than 15 and 50, respectively. After intravenous administration at the dose of 2.5 mg/kg, enrofloxacin achieved concentrations several times above the MIC for major pathogen bacteria in plasma, and it may prove useful in the treatment of infectious diseases caused by sensitive pathogens in sheep.