The plasma Ca concentration of the fetus is maintained higher than maternal levels by active placental transport. Ca, Mg and PO4 accumulation by the fetus is mainly associated with skeletal growth. The fetal parathyroid glands are essential for maintenance of elevated plasma Ca, which is necessary for the stimulation of fetal osteoblasts and mineralization of cartilage and osteoid. Fetal thyroparathyroidectomy (TxPTx) results in a decreased activity of the placental Ca pump. The presence of a parathyroid hormone-related protein (PTHrP) has been demonstrated in fetal parathyroid glands and placental tissue. Extracts of fetal parathyroid glands and purified PTHrP, as well as recombinant PTHrP (1-84, 1-108 and 1-141), stimulate Ca and Mg but not PO4 transport across the placenta of TxPTx-ized fetuses perfused with autologous blood in the absence of the fetus. Parathyroid hormone (PTH) and the N-terminal region of PTHrP do not stimulate placental Ca and Mg transport. It is concluded that a mid-molecule region of this novel hormone may be required to stimulate placental Ca transfer and contribute to the regulation of fetal Ca homeostasis.