Radioimmunoassay determinations of calcitonin from blood samples obtained by selective venous catheterization have demonstrated a large peripheral to thyroid vein gradient for this hormone in both normocalcemic and hypercalcemic persons. These findings indicate that in fasting humans the thyroid gland maintains peripheral levels of calcitonin by actively secreting the hormone, and are consistent with the suggestion that the role of plasma calcitonin is of physiologic significance.