Cord blood levels of nitrate/nitrite, as a measure of nitric oxide (NO), are generally increased in preeclampsia. As L-arginine is the precursor for NO synthesis, we hypothesized that L-arginine transport across the syncytiotrophoblast basal plasma membrane (BM) of placentas from preeclamptic patients is also increased. Glutamine-sensitive and -insensitive [ 3H]L-arginine uptakes into BM vesicles were measured and expressed as femtomoles per milligram of protein per minute. Total L-arginine uptake was 418 ± 15 (mean ± SEM; n = 9) in BM from control placentas (CBM) and 495 ± 27 (n = 7) in BM from preeclamptic placentas (PE BM; P < 0.05, by two-tailed t test). Glutamine insensitive (system y+) uptake was 45 ± 3 (n = 6) in CBM, with a significantly higher uptake of 97 ± 23 (n = 5) into PE BM (P < 0.05, by two-tailed t test). There was no significant difference in glutamine-sensitive uptake between the two groups. The expression of mRNA for human cationic amino acid transporter (hCAT) 1, 2, and 4 (system y+ genes) and 4F2hc (heavy chain of system y +L) was not different in homogenates of whole placenta from the two groups. Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM. These data suggest increased activity of the BM system y+ cationic amino acid transporter in preeclampsia. If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS.