Background: The rates of maternal and fetal blood flow through the placenta are known to be rate limiting for the delivery of oxygen to the fetus. However, the extent to which flow may be limiting for amino acid transfer has not previously been investigated. Amino acid transport has not been regarded to be flow dependent. However the activity of amino acid exchangers and facilitated transporters in the placenta will be affected by trans-membrane gradients and so their activity may be linked to flow. Methods: Human placentas were collected from term, uncomplicated pregnancies delivered at the Princess Anne Hospital, with written informed consent. The placental uptake and transfer of 14C-phenylalanine was determined in isolated perfused human placental cotyledons from 5 placentas at different maternal and fetal flow rates. Maternal flow was set at 10, 14 and 18 ml/min for one hour each. At each maternal flow rate, a fetal flow rate was set at 3, 6 and 9 ml/min for 20 minutes each. 14C-phenylalanine concentrations in the maternal and fetal venous effluent were measured by liquid scintillation counting. Results were analysed by a two way ANOVA. Results: Placental uptake of 14C-phenylalanine (mol/min) increased with increasing maternal (P=0.011) but not fetal flow (P=0.41). The concentration of 14C-phenylalanine (mol/l) in the fetal vein was higher at low fetal flow rates (P<0.001) but was not associated with maternal flow (P=0.41). Total delivery (mol/min) of 14C-phenylalanine to the fetal-side was not associated with fetal (P=0.95) or maternal flow (P=0.95). There were no significant interactions between maternal and fetal flow rate on 14C-phenylalanine concentration, uptake or transfer. Conclusion: This study suggests that placental transfer of 14C-phenylalanine is independent of maternal or fetal flow and is limited by other factors. As increased uptake at higher maternal flow rates did not correspond to increased transfer, this suggests that 14C-phenylalanine transfer may be limited at the basal plasma membrane.