Because of the possible administration of high dose rates of zinc compounds to ruminants as a prophylactic measure against facial eczema, the toxicities and pathological effects of certain zinc compounds have been examined in sheep and cattle. At daily dose rates of zinc as low as 15 mg Zn/kg b.wt. lesions of zinc toxicity were observed but these were not always accompanied by clinical signs. After long term administration, zinc oxide treated sheep were heavier and fatter than controls. At higher dose rates of zinc oxide, body weight losses were recorded. Zinc sulphate caused greater weight loss, more deaths, more severe lesions and higher serum and organ zinc concentrations than zinc oxide which in turn was more toxic than zinc EDTA. Single zinc EDTA administrations resulted in more rapid rises and falls in serum zinc concentration and higher urinary zinc concentrations than the other two forms of zinc. Although most toxicity trials were conducted using sheep, some cattle were also dosed and these findings suggested that cattle react to high dose rates of zinc similarly to sheep. The administration of zinc sulphate solutions to sheep and cattle by drenching gun caused abomasitis and other lesions of zinc toxicity were more severe and elevations of organ zinc higher than when the zinc was given by intraruminal intubation. Zinc solutions were shown to stimulate the reticular groove reflex causing the bolus to be deposited in the abomasum where it caused severe mucosal damage. When, for the same drenched dose rate of zinc sulphate, alternative combinations of volume and concentration were tried, it was shown that the greater volume alternative was more important than greater concentration in the production of zinc toxicity. Single intraruminal doses of zinc sulphate (100 and 200 mg Zn/kg b.wt) caused reductions in food intake, elevations of duodenal pH and the secretion of acid from isolated abomasal pouches was doubled. All forms of zinc administered caused lesions of the exocrine pancreas comprising duct necrosis and inflammation, acinar cell degeneration and inter-and intralobular fibrosis. The characteristics and chronology of these lesions suggested that the primary site of zinc-induced pancreopathy is in the pancreatic ductule. Severe pancreatic lesions caused by zinc oxide resulted in marked reductions of flow rates of pancreatic juice and in the concentration of protein and amylase in pancreatic juice. Although pancreatic bicarbonate output decreased, the concentration of bicarbonate in pancreatic juice was unaffected. In subacute or chronic zinc sulphate toxicity of sheep and cattle there were often lesions indicative of one or more haemolytic episode. These consisted of a nephrosis and focal hepatic necrosis. Additional lesions seen in zinc toxicity were a periacinar fatty change, atrophy of ruminal papillae with epithelial metaplasia and a thymic atrophy. When zinc was added to the milk of sucking lambs (0 .2 g Zn ℓ) the typical pancreopathy of zinc toxicity occurred and, in addition, severe nephrosis with extremely high concentrations of kidney zinc were found. Zinc concentrations were increased considerably in liver, kidney and pancreas, but not muscle, in all experiments. After cessation of zinc dosing zinc concentrations in these organs rapidly returned to normal. Zinc was shown to interfere with selenium metabolism but this did not appear to be responsible for any of the lesions recognised in zinc toxicity. The addition of zinc sulphate to the sole drinking water (0.25, 0.5 and 1.0 g Zn/ℓ water) of yearling cattle for nine weeks reduced water consumption. This effect was greatest soon after the introduction of zinc to the drinking water. At the highest zinc concentration, there were pancreatic lesions in all cattle and less body weight gains than in controls.