We report the effects of alendronate on phosphate homeostasis in two patients. In a woman with postmenopausal osteoporosis, the infusion of alendronate (7.5 mg intravenously daily for 4 consecutive days) was not associated with secondary hyperparathyroidism despite a reduction in serum calcium. This was associated with a rise in serum phosphate and TmP/GFR. This response contrasted with those observed in 14 other patients with osteoporosis, in whom PTH rose significantly following the infusion of alendronate in association with a significant fall in serum phosphate and TmP/GFR. The second patient, a woman with Paget's disease, was treated with intravenous alendronate (10 mg daily for 5 consecutive days) on two occasions for relapse of disease activity. On the first occasion there was a 150% rise in serum PTH associated with a fall in serum phosphate and TmP/GFR. On the second occasion, when the rise in serum PTH was less marked, there was a rise in serum phosphate and TmP/GFR. We conclude that alendronate may increase renal tubular reabsorption of phosphate, but that this effect is usually offset by secondary hyperparathyroidism.