ABSTRACT. Control of maternofetal calcium transfer across the in situ perfused rat placenta at day 21 of gestation (term 23 d) was investigated in both intact fetuses and those parathyroidectomized by decapitation on day 19. Decapitation resulted in significant fetal hypocalcemia. Injection of fetuses subcutaneously through the uterine wall with 0.43 ~g bovine (b) PTH(1-84), 20 ng 1,25(OH),D3 or 10 FL of the appropriate diluent resulted 2 h later in a raised fetal blood ionized Ca concentration only with bPTH(1-84) in both normal and decapitated fetuses. Fetal decapitation caused a significant ( p < 0.001) fall in the clearance of 45Ca across the placenta (KmP5Ca), which was significantly ( p < 0.05) reversed after fetal bPTH(1-84) and 1,25 dihydroxy vitamin D3 (1,25(0H)2 D3) injection, but not back to normal levels. There was no effect of either hormone on K,P5Ca in placentas from intact fetuses, or on KmfSICr-EDTA (used as an extracellular marker) in either group. When 4 ng/mL r[Nle8321,Ty?4] PTH(1-34), 50 pg/mL 1,25(OH),D3 or the appropriate diluent was perfused through placentas the only response observed was a significant (p < 0.05) increase in KmP5Ca with 1,25(OH),D3 perfusion in placentas from decapitated fetuses, KmfSICr-EDTA being unchanged. Finally, perfusion with M forskolin (an activator of adenylate cyclase) stimulated KmP5Ca in placentas from both normal and decapitated fetuses. Although there was also some effect on KmfSICr-EDTA in the latter, there was none in the placentas from normal fetuses, and here the effect on KmP5Ca was dose dependent with an initial response at M. It is therefore suggested that fetal PTH and 1,25(0H),D3 may play a permissive role in the control of maternofetal calcium transfer and that other hormones which act via CAMP may be involved in the acute regulation of calcium transfer under normal conditions. (Pediatr Res 26: 109-115,1989) In the sheep there is evidence that prolactin may stimulate and calcitonin reduce net maternofetal calcium transfer (1, 2), and studies on fetally perfused sheep placenta suggests that PTHrP may stimulate calcium transfer (3). There have been few direct studies in other species (4) although fetal calcium homeostasis also appears to be autonomous in the rat. Thus PTH (5) and calcitonin (6) do not appear to cross the rat placenta and are presumably of fetal or placental (7, 8) origin, and the fetal parathyroids (9) and thyroid "C" cells (10) are active in utero.Fetal 1,25(OH)2D3 may be derived from the mother across the placenta (1 l), be produced by the placenta itself (l2), or by the fetal kidney (1 3), although the fall in plasma 1 ,25(OH)2D3 concentration after bilateral nephrectomy of the sheep fetus (14) suggests thatjn this species the fetal kidney is the major source.Stulc and Stulcova (1 5 ) have described a method for perfusing the fetal side of the rat placenta and demonstrated by this method active maternofetal calcium transport quantitatively similar to that found in vivo. We have also recently investigated the passive permeab...