Fura-2-loaded human cytotrophoblasts responded to elevated extracellular Ca2+ concentration ([Ca2+](o)) with monophasic or, in the case of large (>20 mu m) extravillous cells, biphasic elevations in intracellular free Ca2+ ion concentration ([Ca2+](i)) that returned to baseline levels after restoration of control [Ca2+](o). Large extravillous cytotrophoblasts also responded to elevated [Mg2+](o) with transient elevations in [Ca2+](i), consistent with the behaviour of the parathyroid Ca2+-sensing receptor. Expression of the parathyroid Ca2+-sensing receptor in placental cells was confirmed using Northern blot and reverse transcription (RT)-PCR analysis. However, the major transcript in human placental cells (6.2 kb) differed from that expressed by human parathyroid cells (5.6 kb). RT-PCR analysis and DNA sequencing of key PCR products also revealed the presence of a splice variant in placental and parathyroid cells that lacks exon 3.