An investigation of the effects of intravenous administration of thiomolybdate on copper metabolism in chronic Cu-poisoned sheep.

1. Fourteen sheep were dosed repeatedly with a solution of copper sulphate (2 g/l) in order to induce chronic copper poisoning and four similar undosed animals acted as controls 2. Thiomolybdate (TM) was intravenously administered to all control sheep and to all except two of the test sheep. A variety of biochemical factors were studied before and after injections of TM. 3. The direct-reacting Cu, whole-blood Cu and plasma Cu concentrations were elevated in animals given TM injections and at the "haemolytic crisis" of untreated chronic Cu-poisoned animals. But most of the increased Cu observed on injecting TM was insoluble in trichloroacetic acid (TCA) and did not enter erythrocytes. The results indicate that uptake of Cu by erythrocytes is essential for haemolysis to occur and that for this to happen the Cu must be in a direct reacting, TCA-soluble form. 4. Increased amounts of Cu were excreted in the urine at haemolysis and at commencement of TM injections. High levels of direct-reacting Cu were found in plasma at these times. 5. Marked changes were not found in caeruloplasmin activity, packed cell volume or the osmotic fragility of erythrocytes except at haemolysis. TM injection s did no alter these factors in any of the sheep studied.