1. (CU)-C-65/(CU)-C-63 stable-isotope ratios have been measured in blo
od serum after oral administration of the stable isotope (CU)-C-65. Th
e incorporation of the isotope into the plasma protein pool was follow
ed at various times for up to 3 days, The resulting patterns of enrich
ment in healthy control subjects, in Wilson's disease patients and in
heterozygotes for the Wilson's disease gene, were similar in appearanc
e to those found by others using copper radioactive isotopes, After an
initially high enrichment at 2 h after dosage, the Wilson's disease c
ases, in contrast to the control subjects, did not show a secondary ri
se in isotope enrichment of the plasma pool after 72 h, demonstrating
a failure to incorporate copper into caeruloplasmin. The Wilson's dise
ase heterozygotes had variable degrees of impairment of isotope incorp
oration, not always distinguished from those of control subjects. 2. T
he stability of the isotope also permits the copper tracer to be follo
wed for a longer period, Ten healthy subjects were studied for over 40
days, allowing the biological half-time of an oral dose of copper to
be determined (median 18.5 days, 95% confidence interval 14-26 days),
Known heterozygotes for the Wilson's disease gene were found to have a
significantly increased biological half-time for removal of copper fr
om the plasma pool (median 43 days, 95% confidence interval 32-77 days
). 3. The incorporation of (CU)-C-65 in patients with diseases of the
liver (other than Wilson's disease) was found to be similar to that in
control subjects, aiding differential diagnosis.