1. A comparison has been made of the handling of radioactive copper by patients with Wilson's disease, patients with primary biliary cirrhosis and a small control group. The object of this study has been to assess the influence of an expanded hepatic pool of copper on the incorporation of radioactive copper into caeruloplasmin.

2. Studies with 67Cu have shown that radioactivity disappears steadily from the plasma of patients with Wilson's disease for periods up to 296 h. Both in patients with primary biliary cirrhosis and in controls, a well-marked secondary rise occurs as radioactive copper is incorporated into caeruloplasmin.

3. Caeruloplasmin has been isolated from the serum of one control subject, one patient with primary biliary cirrhosis and one with Wilson's disease. Of the plasma radioactivity 90% was present in the caeruloplasmin of the control subject and the patient with primary biliary cirrhosis; only 27% was found in the caeruloplasmin of the patient with Wilson's disease.

4. Turnover time for liver copper has been determined; in the control subjects it was of the order of 20–30 days, in the patients with primary biliary cirrhosis it was between 600 and 700 days, in Wilson's disease the time exceeded 1800 days. In all cases the turnover time for radioactive copper was significantly less.

5. We conclude (a) that newly arrived radioactive copper is preferentially handled in the presence of copper overload and (b) dilution of radioactive copper in an expanded hepatic pool of the metal cannot alone account for the delayed incorporation found in patients with Wilson's disease.

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