The purpose of this study was to determine whether there is any relationship between the activity of cationic amino acid transporters in the microvillous plasma membrane (MVM) of the syncytiotrophoblast and the oxygenation of the uteroplacental unit. Oxygenation data were obtained at the time of caesarean section from the uterine veins, the maternal radial artery and the umbilical vessels of 7 normal (AGA) and 13 intrauterine growth restricted (IUGR) pregnancies. Microvillous plasma membranes were isolated from the same placentas and the activity of the system y(+) and y(+)L cationic amino acid transporters determined by measuring (3)H- l -arginine uptake in the presence and absence of l -glutamine. In IUGR pregnancies uterine venous Po(2) was significantly higher (AGA=44.7+/-8.0 mmHg; IUGR=57.2+/-2.3 mmHg, P< 0.05) and umbilical venous Po(2) was significantly lower (AGA=33.4+/-3.0 mmHg; IUGR=25.1+/-2.0 mmHg, P< 0.05) than in AGA pregnancies. System y(+)L activity, but not system y(+) activity, was inversely correlated with uterine venous Po(2) (P< 0.01; r(2)=0.4) in AGA and IUGR pregnancies. In IUGR pregnancies without associated maternal pre-eclampsia, y(+)L activity, but not y(+) activity, was also directly related to the umbilical O(2) content difference (P< 0.01; r(2)=0.9). A significant negative correlation was found between system y(+) and the umbilical O(2) content difference in AGA pregnancies (P< 0.01; r(2)=0.9). Our data are consistent with the hypothesis that in IUGR fetuses uterine oxygenation is not reduced and can be increased. The inverse correlation between system y(+)L activity and uterine venous Po(2) and the correlations with umbilical venous-arterial O(2) content difference suggest a relationship between cationic amino acid transporter activity and oxygen tension in the uteroplacental unit.