Evidence is growing that the range of zinc stable isotope compositions, represented by the deviation of 66 Zn in permil units relative to a standard and expressed as d 66 Zn, is larger in organic matter than in inorganic material. This study reports the variations of d 66 Zn in various organs of sheep raised on a controlled diet. Zinc was purified by anion-exchange chromatography. The Zn concentrations and Zn stable isotope compositions were determined by quadrupole inductively coupled plasma mass spectrometry and multi-collector inductively coupled plasma mass spectrometry, respectively. The data show that d 66 Zn variability exceeds 1%, with bone, muscle, serum and urine enriched in the heavy isotopes, and feces, red blood cells, kidney and liver enriched in light isotopes, all relative to the diet value. The 66 Zn enrichment of the circulating serum reservoir is likely to take place in the digestive tract, probably through the preferential binding of lighter isotopes with phytic acid, which is known to control the uptake of metallic elements. Mass balance calculations suggest that the 66 Zn depletion between diet and feces, which is not balanced by any other outward flux, leads to a secular isotopic drift in serum. A simple time-dependent two-box model, involving the gastrointestinal tract on the one hand and the muscle and bone on the other, predicts that the maximum 66 Zn enrichment, which equals the difference in d 66 Zn between diet and bulk ($0.25%), is reached after about ten years. Therefore, a better understanding of the variations of natural abundance of Zn isotopes in animals and humans will probably bring new perspectives for the assessment of their Zn status. Copyright # 2010 John Wiley & Sons, Ltd.Zinc is an essential element for living organisms as it is required for the activity of >300 enzymes. 1 It has five stable isotopes, 64 Zn, 66 Zn, 67 Zn, 68 Zn and 70 Zn, with average natural abundances of 48.6, 27.9, 4.1, 18.8 and 0.6%, respectively. Although still at a very early stage, studies of the variations of Zn stable isotope ratios a in vegetal tissues show d 66 Zn values ranging from À0.6% to 1.4% in plants, [2][3][4] exceeding the variability known for geological terrestrial materials ($ À0.2% to 0.6%; for reviews, see 5,6 ). Such a large variation in d 66 Zn values is thought to be the result of massdependent fractionation during diffusion processes, first from growth media to plant, and then among plant physiological components (seed, stem and leaf). There is little data available for d 66 Zn values in animal tissues.Maréchal et al. 7 report values for standard bulk plankton (CRM 414), lobster liver (CRM TORT-2) and mussel tissue (CRM 278) that are 66 Zn-enriched by 0.07%, 0.16% and 0.47%, respectively, relative to English Channel seawater (0.35 AE 0.08% 8 ). Values of 0.50 AE 0.03% for standard bovine muscle (SRM 8414) and bovine liver (SRM 1577a) were reported by Ohno et al. 9 An average d 66 Zn value of 0.40 AE 0.15% (n ¼ 9) can be calculated for human blood using data published by ...