1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64Cu.
2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of normal subjects by dialysis and gel-chromatography studies.
3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that of complexes formed by secretions of normal subjects.
4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity for copper than the other alimentary secretions or EDTA at a concentration of 10 mmol/l.
5. Absorption of 64Cu from 64Cu-labelled saliva, gastric juice or l-histidine solution (100 mmol/l) administered intraduodenally into groups of rats was similar to that observed in a control series given [64Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64Cu from labelled hepatic and gall-bladder bile was significantly reduced.
6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen may represent a balance between the influence of dietary chelates, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile.