Intrauterine growth restriction (IUGR) is characterized by a reduction in fetal plasma concentrations of a number of essential amino acids. Whether this is caused by impaired placental transport is unknown. We studied transport of leucine and lysine in syncytiotrophoblast microvillous (MVM) and basal membrane (BM) vesicles isolated from uncomplicated (control) and IUGR pregnancies. In addition, we investigated the possibility that leucine uptake is stimulated by an outwardly directed glycine gradient. Uptake of 3H-L-lysine (0.1 microM) and 3H-L-leucine (0.25 microM) was studied at 37 degrees C using rapid filtration techniques. In IUGR, mediated uptake of lysine was reduced by 44% (p < 0.05) in BM and uptake of leucine was lower in both MVM (-46%, p < 0.05) and BM (-38%, p < 0.05) compared with control vesicles. Intravesicular glycine (2 mM) increased the uptake of leucine by 98% in MVM (p < 0.05). These data suggest that the activity of placental transporters for cationic and neutral amino acids is reduced in IUGR. We speculate that a reduced glycine gradient in the placenta in IUGR, due to reduction in system A activity, will impair leucine transport to the fetus, providing an additional mechanism for reduced placental transport of leucine in IUGR.