Subjects (109) with symptomatic Paget's disease of bone were treated with 5, 10, or 20 mg of sodium etidronate (EHDP)/kg body weight - day for 6 to 24 months. Significant decreases in serum alkaline phosphatase and urinary hydroxyproline were noted after 6 months of therapy; no significant further improvement resulted after prolonged therapy. Some patients maintained biochemical remission after withdrawal of EHDP but others showed a relapse, related primarily to the pretreatment severity. Clinical improvement was noted in 61% of the patients. Similar findings were seen after a second course of EHDP. No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day. In patients treated with 10 or 20 mg of EHDP/kg body weight - day, severe diarrhea, bone pain, and nontraumatic fractures were noted in 3, 13, and 12 patients respectively. Quantitative histomorphometry showed mineralization delay in patients receiving 10 or 20 mg of EHDP/kg body weight - day but not in those receiving 5 mg/kg body weight - day. Five milligrams of EHDP/kg body weight - day was effective and appears to be safer than the higher doses.