The relationship between the reproductive system and calcitonin secretion was investigated in the rat. Plasma calcitonin [CT] levels were measured in normal and ovariectomized rats at basal levels and during Ca challenge. Sensitivity of the normal and operated animals to exogenous Ct administration was studied. Ovariectomy leads to a transient fall in both CT levels and in the secretion of the hormone in response to a Ca challenge. A greater sensitivity of ovariectomized animals to salmon CT is maintained after the return to normal of both the basal level of the hormone and of its secretion in response to a Ca challenge. Estrogen substitutive therapy does restore CT levels and antagonizes the action of exogenously administered CT in ovariectomized rats. Ovarian factors other than estrogens may directly or indirectly affect CT secretion.