Concentrations of oxytetracycline (OTC) in serum and tissue-cage fluid (TCF) from subcutaneous tissue-cages were determined after single and repeated intravenous and intramuscular doses of 10 mg/kg to calves. Intravenous administration resulted in higher levels, and greater area under curve (AUC) in TCF, than did intramuscular administration. However, the penetration measured as the ratio of AUC in TCF to AUC in serum was equal, and therefore independent of the route of administration. A linear relationship between AUC in serum and AUC in TCF could be demonstrated. Half-lives of OTC in serum were 4.9 +/- 3.1 h after intravenous, and 6.1 +/- 2.0 h after intramuscular administration. In TCF the half-lives were 21.5 +/- 4.4 h and 24.5 +/- 11.5 h after intravenous and intramuscular administration, respectively. Repeated dosing resulted in accumulation of OTC in TCF. Lesser accumulation in older cages indicated altered characteristics of the cages with the passage of time. In serum, no substantial accumulation was seen after repeated i.v. dosing until the dosing interval was shortened to 6 h.