On a molar basis, the human fetus requires more glycine than any other amino acid but direct placental transfer of glycine is not thought sufficient to meet fetal demand (Widdowson et al. 1979). _L-Serine is a major metabolic source of glycine for the fetal sheep (Chung et al. 1998) and this may also be true in human pregnancy. We have characterised the amino acid transport systems involved in the uptake of serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine. Term placentas were collected within 30 min of delivery from women who had provided written informed consent. Using standard techniques (3,4), we prepared microvillous membrane (MVM) vesicles and measured uptakes of ¹⁴C-_L-serine and ³H-glycine into these vesicles at room temperature. _L-Serine uptakes were performed for 15 s (characterisation) or 20 s (kinetics) and glycine uptakes were performed for 60 s, times when uptake had been shown to be linear. Na⁺-dependent uptake accounted for 40 ± 4% (mean ± SEM, n=14) of _L-serine uptake, of which 29 ± 10% was attributable to system A (MeAIB inhibitable). Na⁺-independent uptake accounted for 60 ± 3% of _L-serine uptake, of which 51 ± 3% was attributable to system L (BCH inhibitable). BCH inhibitable _L-serine uptake was inhibited by 1 mM _L-alanine, _L-threonine and _L-asparagine, which are substrates of LAT 2, but not LAT 1 or LAT 3, suggesting that the uptake is mediated by the LAT 2 isoform of system L. Uptake kinetics were determined for _L-serine and glycine (see figure 1) and analysed using SimFit ver. 5.5 (www.simfit.man.ac.uk). Uptake of _L-serine into MVM vesicles had a V_max of 2.47 ± 0.20 nmol/mg/min and had a K_m of 290 ± 20 μM (mean ± SEM, n=3). Uptake of glycine into MVM vesicles had a V_max of 0.69 ± 0.24 nmol/mg/min and a K_m of 210 ± 32 μM (mean ± SEM, n=4). This indicates that MVM vesicles have a higher uptake capacity for _L-serine than for glycine. This study indicates that MVM placental uptake capacity for _L-serine is substantially greater than for glycine, and that this serine uptake is primarily mediated by system L and system A. If placental transfer, as well as uptake, of _L-serine is also greater than for glycine then fetal conversion of serine to glycine may be a significant source of fetal glycine.