Experiments were carried out to study calcium changes relative to the endogenous secretion of a thyroid principle which has hypocalcemic properties. Several protocols were followed: 1) The serum calcium of parathyroidectomized and thyroparathyroidectomized rats was measured after 10 days on Purina chow. 2) Rats were subjected to peritoneal lavage with a calciumfree rinse as well as one containing 12 mg calcium/ 100 ml, and the calcium transfer into this fluid was measured. 3) Animals were infused with calcium chloride and were bled subsequent to the infusion. Serum samples were analyzed for calcium. 4) Rats were subjected to a single intraperitoneal injection of calcium and changes in the serum calcium were recorded. The results showed that the thyroid gland releases a principle which has the ability to lower the serum calcium of rats. By using animals with functional parathyroid transplants, it was shown that the origin of the principle was not from the parathyroids. The experiments suggest that this hypocalcemic principle not only is released under conditions of varying calcium levels but that it is effective in lowering the serum calcium after its experimental elevation. (Endocrinology76: 103, 1965)