Recent evidence from both humans and mice suggests parathyroid hormone related protein (PTHrP) is a key regulator of placental calcium flux. The PTHrP knockout mouse (PTHrP^-/-) suffers from severe skeletal dysplasia and neonatal morbidity (Karaplis et al., 1994). Using a technique recently devised for artificially perfusing the fetal circulation of the mouse placenta (Bond et al., 2004) we measured unidirectional maternofetal calcium clearance (^CaK_mf) across placentas of PTHrP^-/- versus PTHrP^+/+ and PTHrP^+/- fetuses. Expression of the placental calcium binding protein, calbindin-D_9k was also determined. Heterozygote mice were mated and on day 18 of gestation (term = 19-20d) mice were anaesthetised (i.p. fentanyl citrate/fluanisone: 24 and 750μg) and the uterus delivered into a bath of 40^oC saline. A fetus was selected, the umbilical artery and vein catheterised and perfused with Krebs Ringer (pH 7.4) at 60 μl.min^-1. ⁴⁵CaCl₂ (2μCi/50 μl saline) was injected via a maternal tail vein. Perfusate samples were collected every 5 mins for 45 mins. ^CaK_mf was calculated as: perfusate [⁴⁵Ca] x perfusion rate/maternal plasma [⁴⁵Ca] x placental weight. Calbindin-D_9K protein expression was measured in placentas using Western blotting and signal measured in arbitrary density units. Results for the perfusion are expressed as the mean value over 45 mins as there was a tendency, although not significant, for ^CaK_mf to decline over time in all genotypes. Results are shown in Table 1, Mean±SEM, n=number of litters. ^CaK_mf was significantly higher across the placentas of the PTHrP^-/- relative to the PTHrP^+/- and PTHrP^+/+ fetuses (***P<0.001, repeated measures ANOVA followed by Bonferronis post hoc). Calbindin-D_9k protein expression is possibly increased in the placentas from the PTHrP^-/- fetus (*P<0.07, Kruskal-Wallis). These data provide further evidence that PTHrP has an important role in regulating calcium transport across the placenta and therefore in fetal development, thus emphasising the importance of direct measurements of the unidirectional components of net flux across the placenta. All work was in accordance with the U.K. Animals (Scientific Procedures) Act 1986.