Dichloromethylene diphosphonate (Cl2MDP), a powerful inhibitor of bone resorption, was given (daily dose: 500 mg i.v. for 2 months and then 1600 mg p.o.) to five patients with Paget's disease after 8 months treatment with 50-100 MRC u/day of human calcitonin (CT). During treatment with CT plasma alkaline phosphatase (ALP) and urinary hydroxyproline (HOP) levels fell to about 60% of pretreatment values within the first 2 months in all the patients. Cl2MDP therapy resulted in a further drop of urinary HOP to 20% of baseline values, while serum ALP rose impressively during the first 2 weeks of therapy and then slowly fell to 25% of baseline values. We conclude that Cl2MDP can induce a further biochemical response after the so-called plateau phenomenon to CT and that it may represent the therapy of choice for severe Paget's disease.