Clodronate, an inhibitor of osteoclast function, reduces bone resorption in osteolytic metastases and in multiple myeloma. We have evaluated its ability to decrease bone destruction in patients with multifocal eosinophilic granuloma of the skeleton. Two patients, whose multifocal bone granulomas appeared with a frequency of about 6 months, received 1.6 g day-1 oral clodronate for 6 months. Both patients had a reduction in serum calcium level which was accompanied by a decline in the fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios and a slight increase in parathyroid hormone (PTH) level. Pain relief was observed in both patients. No new bone lesions were seen during the treatment and the old lesions healed. After discontinuing the therapy, however, new painful lesions appeared after 5 years in patient 1 and after 3, 4 and 5 years in patient 2. We suppose that clodronate delayed the appearance of new granulomas.