In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is distributed to both the microvillous membrane (MVM) and the basal membrane (BM) of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in maintaining the electrochemical gradient for Na(+), which represents the driving force for Na(+)-coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na(+)-coupled transporters and contribute to the reduced growth of these fetuses.