Clodronate can be used in animals to prevent the effects of immobilization on bone. For this reason we have studied the effects of this agent on immobilisation bone loss in man. We administered clodronate by mouth to 14 paraplegic patients (400 mg/d, n = 7; 1600 mg/day, n = 7), and compared its effect with a placebo (n = 7). Treatment was given for 100 days, 5-29 days after spinal cord injury. Our results suggest that clodronate, given early after immobilization, prevents the acute bone loss observed in immobilization as judged by its effects on serum and urine calcium and hydroxyproline, bone mineral content, trabecular bone volume, and the number of osteoclasts present in bone. No mineralization defect or other side-effects were observed during or after treatment. In addition, a total of 70 patients, with comparable degrees of immobilization, were studied with a variety of antiosteoclastic drugs comprising controls (n = 16), etidronate (n = 20), salmon calcitonin (n = 20) and clodronate 400 mg/d (n = 7) or 1600 mg/d (n = 7). Clodronate, at the dose of 1600 mg/d appeared the most effective drug on bone resorption, together with calcitonin. Unlike calcitonin, clodronate can be administered orally. The mineralisation defects observed during prolonged treatment with etidronate at high doses were not observed with clodronate. We conclude that clodronate 1600 mg/d is a promising agent for the treatment of bone loss and the resorptive hypercalcaemia and hypercalciuria noted in immobilisation.