A deficit of immunoreactive calcitonin (iCT) has been found in women with postmenopausal osteoporosis (PM-OP), however, recent studies assessing the monomeric fraction of calcitonin (exCT) do not seem to confirm these findings. We have measured serum levels of iCT by radioimmunoassay (RIA) and exCT (chromatography and RIA) at 0, 5, 10, and 20 minutes after the i.v. infusion of 2 mg calcium/kg body weight in four different groups of women: (1) 12 healthy premenopausal women (HPM), (2) 16 early postmenopausal women (EPM), (3) 16 postmenopausal women within more than 2 years of menopause (LPM), and (4) 24 women with PM-OP. In the HPM group, iCT levels increased significantly 5 and 10 minutes after finishing the calcium infusion (P less than 0.05); this did not occur in the other three groups. The exCT levels in the HPM and LPM groups showed a significantly greater increase than in the EPM and PM-OP groups at 5 minutes (P less than 0.05) and at 10 and 20 minutes (P less than 0.01) after infusion. The behavior of the PM-OP and EPM groups was similar throughout the study. We conclude that there is a calcitonin reserve deficiency in the first years after menopause, which recovers later. This hormone deficiency could explain the accelerated bone loss that takes place at this time of life. The patients with PM-OP also show this deficit, and this may play an ethiopathogenic role in the production of the disease.