Fetal growth depends on the mother’s nutrient supply, which, in turn, depends on the size and nutrient transfer capacity of the placenta (1). The mouse placenta transfers nutrients by simple and facilitated diffusion and by active transport across the labyrinthine interhaemal membrane (LIM)(2,3). From formation of the placenta at E9 until E16, both the mouse fetus and placenta grow continually. Thereafter, the fetus continues to grow but placental weight plateaus. In normal litters near term, fetal and placental weights vary widely and often relate poorly to one another suggesting that the efficiency of placental nutrient transfer varies within litters. Placental efficiency, estimated as the feto-placental weight (fp) ratio, can be manipulated experimentally by altering gene expression or nutrient intake during pregnancy (4,5). For example, the small placenta of mice deficient in placental-specific Igf2 is more efficient and transfers more glucose and amino acids than the normally sized wildtype placenta in late gestation (4). Hence, this study investigated the morphology and nutrient transfer capacity of the lightest and heaviest placentas within normal mouse litters at E16 and E19, (term= E20.5). Unidirectional materno-fetal transfer of radioactively labelled, non-metabolisable molecules was measured in vivo (4). Stereology was used to quantify placental compartment volumes and blood vessel volumes. Furthermore, LIM surface area and thickness were measured to determine a theoretical diffusion capacity (TDC)(3). The fp ratio was greater in the lightest placentas at both E16 and E19. Fetal body weight was significantly less with a light than heavy placenta at E16 but was similar in the two placenta groups at E19. Transport of C14-methyl-aminoisobutyric acid (MeAIB) per gram of placenta was greater in the lightest than heaviest placentas at both gestational ages. In contrast, passive and facilitated diffusion, measured using C14-inulin and C14-methyl-glucose respectively, were similar in the lightest and heaviest placentas at E16 and E19, when values were expressed per gram placenta. At E16 per unit volume of placenta, the lightest placentas consisted of a greater % of Lz than the heaviest placentas at E16 but not at E19. At E16 and E19, surface area and thickness of the LIM was equal in the lightest and heaviest placentas. Hence, the lightest placentas have the same TDC as the heaviest placentas at both gestational ages. These data suggest that the small normal placenta may respond to the growth demands of the fetus and upregulate its nutrient transport capacity by increasing the surface area for nutrient exchange and/or the abundance of amino acid transporters per unit volume of Lz. Thus, the lightest placentas are more efficient and can support a similar fetal mass as the biggest placentas in a litter. Acknowledgements: This project is funded by the BBSRC. Reference 1 : Fowden AL et al. (2006) J Physiol 572, 5-15Reference 2 : Coan PM et al. (2005) J Anat 207, 783-796Reference 3 : Coan PM et al. (2004) Biol Reprod 70, 1806-1813Reference 4 : Constancia M et al. (2005) PNAS 102, 19219-19224Reference 5 : Fernandez-Twinn DS et al. (2003) Br J Nut 90, 815-822