To determine the mechanism by which calcitonin acutely decreses bone resorption in man, salmon or human calcitonin was administered intravenously to five patients with Paget's disease of bone immediately after an iliac crest bone biopsy. After 30 min an adjacent bone biopsy was taken and both were evaluated by light and electron microscopy. The results indicated that calcitonin both decreases the number of osteoclasts and alters the ultrastructure of these cells. These acute effects of calcitonin on osteociasts confirm findings in other species and provide evidence in man that calcitonin, at least in part, retards bone resorption by inhibiting osteoclastic activity.