The depletion profile of oxytetracycline was studied in healthy sheep after intramuscular administration of Oxysentin 100, given at a dose of 10 mg oxytetracycline per kg body weight once daily for 5 consecutive days. Five medicated sheep were slaughtered at 0, 2, 4, 6, 9 and 12 days postmedication, and injection site, muscle, fat, liver and kidney tissues were sampled and analysed using a liquid chromatographic method, which was fully validated for oxytetracycline and 4-epi-oxytetracycline. At day 0 postmedication, the concentrations of oxytetracycline marker residue (sum of oxytetracycline and 4-epi-oxytetracycline) in all tissues examined were at the mg/kg level. At day 2 postmedication, the concentrations of oxytetracycline marker residue in all injection site and kidney samples examined were higher than the corresponding maximum residue limits (MRLs) established by the European Union, while the concentrations in muscle and liver tissues of two and three out of five animals examined, respectively, were below the corresponding MRLs. At days 4 and 6 postmedication, concentrations of oxytetracycline marker residue above the MRLs were found only in the injection site, whereas at day 9 postmedication, all observations were below the corresponding MRLs.