1. An intravenous infusion of calcitonin produced a sudden increase of plasma radioactivity after intravenous administration of 47Ca in man. 2. This effect was noted a few minutes before the well-known decrease of plasma calcium concentration. 3. A mathematical evaluation of this phenomenon demonstrated that: (a) it was significant in normal subjects, provided patients were given calcitonin 60–360 min after the intravenous injection of 47Ca; (b) it was generally not significant in patients with senile osteoporosis or osteomalacia; (c) it was particularly evident in patients with generalized Paget's disease or multiple myeloma. 4. Surface measurements performed on soft tissues and bone demonstrated a transient, simultaneous decrease of 47Ca radioactivity from bone. 5. The increase in plasma radioactivity implies a shift of 47Ca from reservoirs with high specific radioactivity, possibly bone cells, to the circulation. 6. According to these data two different mechanisms of action of calcitonin could be considered: an early effect on bone cells producing a shift of calcium to the circulation, and the well-known later hypocalcaemic effect through diminution of bone resorption.