Study objectives were to determine zilpaterol residues in urine and tissues of sheep fed dietary zilpaterol HCl, at levels commensurate with feed contamination, using common and novel screening and quantitative analytical methods. Sheep (50.0 ± 2.7 kg) were offered feed (1.75 kg/d) containing 0.0075 (L), 0.075 (M), or 0.75 (H) mg kg −1 of zilpaterol for 12 days and were slaughtered with 0-day (L-0, M-0, H-0; n = 4 each) or 3-day (H-3; n = 4) withdrawal periods. Rapid immunochromatographic assays (ICA) consistently detected urinary zilpaterol (LOD = 1.7 ng mL −1) in L-0 (54.2%), M-0 (96.0%), and the H-0 (100%) treatment groups but only detected zilpaterol in tissues (LOD~2.4 ng g −1) from the H-0 group. Advanced MS-based technologies detected zilpaterol in some, but not all, tissues of M-0, H-0, L-0, and H-3 sheep. Analytical techniques commonly used to ensure compliance with show-animal rules, import/export guidelines, and regulatory statutes routinely detected residues in animals exposed to zilpaterol at doses insufficient to elicit growth responses.