The major function of calcitonin in man appears to be the prevention of excessive or unwanted bone resorption. There is a marked sex difference in circulating levels, with a relative deficiency in women. As calcitonin secretion in young women is known to be increased by estrogens, long periods of estrogen lack - such as the postmenopause - are possibly associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially as the latter is believed to be due to excessive bone resorption. We have studied the effects of three exogenous estrogens on the circulating levels in postmenopausal women of calcitonin, parathyroid hormone, the vitamin D metabolites 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D, and calcium and phosphate. The most striking finding was a sharp rise in the plasma levels of calcitonin. Estrogens are known to prevent postmenopausal bone loss but the mechanism of action remains obscure. We suggest that the beneficial effects of estrogens could be mediated, at least in part, through control of calcitonin secretion. Thus calcitonin may prove effective in the prevention of postmenopausal bone loss and its role in the treatment of established osteoporosis warrants further evaluation.