Dichloromethylene diphosphonate (Cl2MDP, or clodronate disodium) is one of the most potent of the known diphosphonates as an inhibitor of bone resorption and differs from EHDP in that it does not inhibit skeletal mineralization. It is one of the second generation diphosphonates now undergoing clinical evaluation. In the study described here Cl2MDP was given by mouth (800-1600 mg/day for 6 months) to 35 patients with symptomatic Paget's disease of bone. Cl2MDP induced a marked fall in serum alkaline phosphatase and urinary hydroxyproline to normal or near normal values in all patients. This was accompanied by clinical improvement in all but 4 patients. Cl2MDP appears to be another effective oral drug for the treatment of Paget's disease of bone and compares favorably with the calcitonins and EHDP.