The disposition kinetics of enrofloxacin at a single dose of 5 mg/kg body weight were determined in clinically healthy captive-reared estuarine crocodiles (Crocodylus porosus) after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Enrofloxacin plasma concentrations were determined by diode array detection–high-performance liquid chromatography (limit of detection/limit of quantitation: 0.05 µg/ml). Data were subjected to noncompartmental analysis. The integrated pharmacokinetic-pharmacodynamic (PK-PD) variables showed that optimal area under the curve from the time of dosing to 24 hr:minimal inhibitory concentration (MIC) (>125) and peak plasma concentrations:MIC (>8) ratios, as reported for concentration-dependent bactericidal antimicrobials like fluoroquinolones, were achievable with both a single i.v. or i.m. dose for susceptible microorganisms with MIC values of ≤0.5 µg/ml, while the relatively slow onset of peak time allowed an effective plasma drug level only on day 3. The persistence of useful plasma concentrations indicated the possibility of redosing every 3 day for parenteral routes of administration, while further studies are needed for the oral route. Nevertheless, the absence of adverse reactions in the animals following i.v., i.m., or p.o. administration of enrofloxacin after a single dose of 5 mg/kg indicates the possibility of its safe and effective clinical use in captive estuarine crocodiles.