Abstract Objectives To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single IV and IM administration of enrofloxacin and tissue residues after serial daily IM administration of enrofloxacin in pigs. Animals 20 healthy male pigs. Procedure 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single IV and IM administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, IM for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle. Results Mean (± SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64 ± 1.49 and 12.77 ±2.15 hours, respectively, after IV administration and 12.06 ± 0.68 and 17.15 ± 1.04 hours, respectively, after IM administration. Half-life at α phase of enrofloxacin was 0.23 ± 0.05 and 1.94 ± 0.70 hours for IV and IM administration, respectively. Maximal plasma concentration was 1.17 ± 0.23 µg/ml, and interval from injection until maximum concentration was 1.81 ± 0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 µg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues. Conclusions and Clinical Relevance Enrofloxacin administered IM at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues. (Am J Vet Res 1999;60:1377–1382)