To investigate the relation between the hypocalcemic activity of thyrocalcitonin and the rate of bone resorption, the quantitative effect of exogenous thyrocalcitonin was studied in rats in which the rate of bone resorption was altered by thyroparathyroidectomy and by the administration of calcium salts, parathyroid extract or vitamin D₃. In sham-operated rats made hypercalcemic by the oral administration of CaCl₃, thyrocalcitonin had no significant hypocalcemic activity. In thyroparathyroidectomized rats given oral CaCl₂, a full Hypocalcemic response to thyrocalcitonin, of 1.49 mEq/1, occurred. In sham-operated and thyroparathyroidectomized rats made hypercalcemic by the administration of parathyroid extract, thyrocalcitonin caused mean decreases in the plasma concentration of calcium of 0.83 and 1.47 mEq/1, respectively. In hypercalcemia produced by the administration of a single dose of 10⁵ USP U of vitamin D³, sham-operated and thyroparathyroidectomized rats showed mean decreases in the plasma concentration of calcium of 1.32 and 1.24 mEq/1, respectively, during thyrocalcitonin administration. A similar hypocalcemic response was seen in thyroparathyroidectomized rats given a 10-fold greater dose of vitamin D³. In collateral studies of the release of ⁸⁵Sr from the skeleton, thyroparathyroidectomy decreased, and vitamin D₃ administration markedly increased, the ratio of urinary ⁸⁵Sr to tibial ⁸⁵Sr. The administration of thyrocalcitonin produced decreases in the excretion of ⁸⁵Sr which were parallel to the control values for the ratio of urinary ⁸⁵Sr to tibial ⁸⁵Sr. These data indicate that the degree to which thyrocalcitonin can inhibit bone resorption is dependent upon the prevailing rate of bone resorption. This characteristic of thyrocalcitonin action may be significant in the treatment of human hypercalcemia with thyrocalcitonin. (Endocrinology81: 599, 1967)