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.