SummaryAmino acid transfer across human placenta has been studied in an in vitro perfusion system. Transfer rates from maternal to fetal circuit of 12 amino acids were about the same when there was a downhill gradient permitting diffusion and active transport. This was termed "maximal transfer rate." Cystine, aspartic acid, and glutamic acid were transferred a t approximately half the rate of the others under these conditions. Measurement of exchange rates with radioactive tracers and with equimolar concentration of amino acids on both sides of the membrane provided a close estimate of maximal transfer rate. Fetal nutrition requires active transfer against a gradient. The rate of active transfer is a fraction of the exchange rate.The ability to establish a transplacental gradient by perfused placenta was investigated with the maternal circuit open and fetal circuit closed (recirculated). The fetal to maternal concentration ratio for D-leucine and antipyrine was 1.0, for L-leucine, 1.5, indicating a stereospecific transport mechanism for leucine. Cradients of 1.56 + 0.11 and 1.62 +. 0.10 were demonstrated for Lalanine and L-lysine, respectively. The establishment of transplacental gradients is a placental function, requiring no assistance using a variety of experimental techniques and experimental animals. Studies in the human have been extremely limited. Slices and fragments of human placenta have been used in vitro to measure amino acid transport (1 I, 12, 16, 19), but the pertinence of the observations to transplacental transport is uncertain. Page et al. (13) have infused D-and L-histidine into several mothers shortly before delivery and have measured the relative concentrations of the stereoisomers in the cord blood at birth. They deduced that L-histidine was transferred more rapidly than the D-isomer. Gaull et al. (7) have studied transfer rates of the sulfur-amino acids during the second trimester in elective abortions.For the past several years, we have been studying transplacental transport by perfusing a n isolated cotyledon of human placenta. Independent maternal and fetal circulations are established permitting the investigation of transfer in either direction. This technique has now been applied to the study of amino acid transport in a n attempt to answer such fundamental questions as the relation of exchange rates to net transfer, the pertinence of in vitro placental uptake studies to transplacental transport, the polarity of the placental membrane, and the possible reserve functions of the large intraplacental concentrations of amino acids. from maternal or fetal factors.The ratios of the exchange rates for the L and D-isomers were MATERIALS AND METHODS determined as a measure of the active, stereospecific transport system. The L:D ratio from the maternal to fetal circulation for PERFUSION TECHNIQUE leucine was 1.64 f 0.19, for alanine 1.78 + 0.49. In the reverse ~h~ technique of dual perfusion of the human placental cotydirection, the ratio for leucine was 1.03. The placental membrane ledon ha...