A long-term trial of etidronate disodium therapy in 93 patients with Paget's disease of bone yielded generally favorable results. Treatment or retreatment was initiated for symptomatic Paget's disease with elevated serum alkaline phosphatase and urinary hydroxyproline values. Improvement occurred in 60 percent of patients even in the presence of secondary osteoarthritis. There appeared to be three types of responses: (1) Patients with prolonged clinical and chemical improvement after a single course of therapy (40 percent); these patients tended to have less active disease on the basis of initial alkaline phosphatase and hydroxyproline values, with suppression to normal in 76 percent of patients after etidronate disodium therapy. (2) Patients with response to retreatment (45 percent); these patients had modest disease on the basis of alkaline phosphatase and hydroxyproline values and required retreatment less often than once a year. (3) Patients with response to retreatment but eventual development of resistance to etidronate disodium (15 percent); these patients had the most severe disease clinically and on the basis of alkaline phosphatase and hydroxyproline values. In this last group, resistance to etidronate disodium (5 mg/kg per day) was common and early, and patients received etidronate disodium more often than one course per year; alkaline phosphatase response was transient, often of less than three months' duration.