Objectives: The mechanisms mediating amino acid transport across the basal membrane and out of the placental syncytiotrophoblast into the fetal circulation are not well understood. Our previous data indicate that amino acid exchangers mediate serine transport into the fetoplacental circulation in exchange for alanine, serine, leucine, threonine, tryptophan and glutamine but not for glutamate. This study characterises amino acid stimulation of leucine transfer into the fetoplacental circulation. Methods: Human placentas (n = 5) were collected within 30 minutes of delivery and an intact cotyledon was perfused with a modified Earl’s bicarbonate buffer. The maternal arterial circulation was perfused with 50 μmol/l L-leucine & glycine, 0.6 μmol/l ¹⁴C-leucine and 20 μmol/l ³H-glycine. Amino acid [12.5 μmol] boluses were administered to the fetal side inflow perfusate. ¹⁴C-leucine and ³H-glycine were measured in maternal and fetal venous samples by dual label liquid scintillation counting. Data (mean ± SEM) were expressed as area under the curve (AUC) and analysed by one-way ANOVA. Results: In the absence of amino acids in the fetal circulation (which are required for exchange) leucine, but not glycine, was transferred to the fetal circulation. Following fetal arterial boluses of specific amino acids transfer of leucine, but not glycine, increased, indicating that transport by exchange was taking place. Leucine exchanged for 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH; a System L substrate), leucine or tryptophan but not serine, glycine, threonine, glutamate or lysine. Conclusion: This study demonstrated that in the perfused human placenta leucine was transported into the fetal circulation by exchange and non-exchange mechanisms and glycine was not actively transported into the fetal circulation. None of the known amino acid transporters are thought to mediate leucine efflux across the basal membrane except for exchangers. It is therefore unclear what is mediating the non-exchange mediated transport. Acknowledgements: This work was funded by The Henry Smith Charity