We have examined the effects of the diphosphonate, clodronate, in 9 haemodialysis patients with severe hyperparathyroid bone disease. Clodronate (300–600 mg infused after dialysis on 5 consecutive occasions) significantly decreased mean serum calcium, phosphate and hydroxyproline. This was associated with an increase in serum immunoassayable parathyroid hormone and activity of alkaline phosphatase. These changes reversed 2–4 weeks after stopping treatment but were sustained when treatment with oral clodronate (1.6 g daily) was supplemented for 2 weeks. Our findings suggest that intravenous clodronate is capable of inhibiting osteoclast-mediated bone resorption in chronic renal failure. The therapeutic potential of clodronate alone or with vitamin D derivatives merits further evaluation, particularly in patients with severe hyperparathyroidism, when the use of D metabolites alone is precluded by the presence of hypercalcaemia.