Three patients with an extensive and severe form of Paget's disease of bone were given porcine thyrocalcitonin every 12 hours for one month or longer. Striking reduction of alkaline phosphatase was observed in three subjects, and decreased hydroxyprolinuria in two. A 16 per cent decrease in cardiac output was measured after 17 weeks of hormone administration to one patient. Evidence of decreased bone turnover persisted for four to five weeks after withdrawal of the hormone from two subjects. Neither tetany nor rebound hypercalcemia occurred. The well tolerated suppressive effects observed suggest a role for thyrocalcitonin in the management of this disorder. PAGET'S disease of bone is an idiopathic disorder characterized by a bizarre and greatly exaggerated skeletal turnover. The early, asymptomatic phase is being encountered more frequently as a result of widespread application of routine chemical and roentgenographic technics. Although attenuation of the disease activity has been observed with the use of aspirin,1 cortisone,2 fluoride3, 4 and mithramycin, an analogue of dactinomycin (actinomycin),5 unacceptable side effects have, in general, prevented their endorsement. Thyrocalcitonin (TCT), a hypocalcemic polypeptide of ultimobranchial origin recently isolated from the thyroid gland,6 has been observed to inhibit osteolysis.7 8 9 10 Moreover, the hypocalcemic effect of the hormone is accentuated when.