Ten patients with symptomatic Paget's disease of bone were treated with mithramycin. Subjective improvement, as demonstrated by complete pain relief and increased activity, was reported by seven patients and partial pain relief was reported by two. Pain persisted in one patient with a co-existing osteogenic sarcoma. No roentgenographic changes were noticed in the involved bones after therapy. Chemically, improvement was demonstrated by reduction of levels of serum alkaline phosphatase and urinary hydroxyproline. Five patients were in positive calcium balance before mithramycin therapy and showed an increase after therapy. Mithramycin administered in the dose of twenty-five micrograms per kilogram of body weight by slow intravenous drip method, once every two to three weeks, was well tolerated and showed suppressive effects on symptomatic Paget's disease of bone, and no hepatic, renal, or myelogenous evidence of toxicity was noticed in the immediate or long-term follow-up in these patients.