Arginine (A) may play a significant role in fetal growth, by stimulating insulin secretion and as a precursor for both polyamine synthesis and nitric oxide production. To determine whether increased maternal plasma A concentrations can enhance delivery of A to the fetus, uterine, umbilical, and net uteroplacental (UP) A uptake rates were measured in 12 pregnant ewes at 129.6 +/- 0.4 d gestation (mean +/- SEM) during normal and after 3 h of increased maternal plasma A concentrations. With a 2.7-fold increase in maternal plasma A concentrations (p < 0.001), there were significant increases in uterine A uptake (13.8 +/- 1.0 to 41.3 +/- 7.7 micromol/min, p < 0.005), umbilical A uptake (3.3 +/- 0.5 to 5.2 +/- 0.8 micromol.min(-1).kg(-1) fetus, p < 0.005), UP A uptake (17.8 +/- 6.2 to 89.2 +/- 20.3 micromol.min(-1).kg(-1) placenta, p < 0.01), fetal arterial A concentration (98.7 +/- 6.3 to 137.1 +/- 9.9 microM, p < 0.001), maternal A disposal rate (143.7 +/- 9.4 to 217.0 +/- 6.7 micromol/min, p < 0.001), fetal A disposal rate (7.9 +/- 0.8 to 9.9 +/- 1.1 micromol.min(-1).kg(-1), p < 0.05), fetal A oxidation rate (1.31 +/- 0.24 to 1.84 +/- 0.36 micromol.min(-1).kg(-1), p < 0.05), and plasma insulin concentration in both fetus (16 +/- 2 to 20 +/- 2 microU/mL, p < 0.001) and mother (24 +/- 3 to 32 +/- 4 microU/mL, p < 0.001). Thus, increased maternal plasma A concentration increases maternal, UP, and fetal A net uptake, and increases insulin secretion in mother and fetus. The 4.2-fold larger increase in UP than net fetal A uptake could represent preferential UP A metabolism relative to fetal A metabolism, relatively limited placental-fetal A transport capacity compared with uterine A uptake capacity, or both; responsible mechanisms remain unknown.