Increased dietary zinc (Zn) influences metallothionein (MT) expression in sheep, which in turn effects changes in the regulation of both Zn and copper (Cu) tissue uptake. Romney wether sheep were given ZnO on a regular basis, as required in protocols for the treatment of facial eczema, at either 12 g ZnO fortnight-1 or 12 g ZnO week-1, and the effect of Zn on MT-Ia and -II mRNA expression in liver, kidney, duodenal, muscle and skin tissue was compared with those of untreated animals. Tissue concentrations of Cu, iron (Fe), manganese (Mn) and Zn were determined by plasma emission spectrometry. Metallothionein-Ia and -II mRNA concentrations were 4 to 9-fold greater in the liver and kidney of dosed sheep compared with untreated animals, but not higher in duodenal, mucscle or skin tissue. Zinc concentrations increased in all tissues, except skin, and were strongly correlated with MT expression. Copper uptake into tissues was not inhibited and it was concluded that this was because duodenum tissue MT mRNA expression was not greatly affected. Relationships between MT-mRNA, MT in liver, and Zn and Cu tissue concentrations are presented and discussed.