1. The bivalent cation-binding agent, cellulose phosphate, together with a low calcium diet was given for 6 days to nine patients with primary hyperparathyroidism subsequently verified at surgery.
2. Urinary calcium fell promptly by 8·4 mmol/24 h, and by 70%, and reached amounts below 4·0 mmol/24 h in five of the nine patients. The magnitude of fall may have been related to increased synthesis of vitamin D by the skin in a sub-tropical environment. Plasma magnesium fell steadily and urinary magnesium fell by 80%.
3. The plasma calcium showed two types of response. In five patients there was no significant change because a reduction in calcium load was offset by a further increase in the already high tubular reabsorption of calcium. In the remaining four patients, the tubular reabsorption of calcium was at a higher level initially and failed to increase further on the experimental regime, with a corresponding fall in plasma calcium.
4. The hypercalcaemia of primary hyperparathyroidism can be explained by increased gastrointestinal absorption and increased renal tubular reabsorption of calcium; net bone resorption makes only a small contribution but an additional factor dependent on the blood-bone equilibrium is not ruled out.
5. Comparison with other published data suggests that the fall in urinary calcium in response to a calcium-depleting regimen is prevented by concurrent depletion of inorganic phosphate and may be enhanced by concurrent depletion of magnesium.
6. Persistence of hypercalcaemia combined with an increase in tubular reabsorption of calcium in response to cellulose phosphate may be of diagnostic value in suspected primary hyperparathyroidism.
7. Cellulose phosphate may be of value in stone prevention in patients with primary hyperparathyroidism who are unsuitable for surgical treatment.