Background: Knowledge on human fetal amino acid (AA) metabolism, largely lacking thus far, is pivotal in improving nutritional strategies for prematurely born infants. Phenylalanine kinetics is of special interest as is debate as to whether neonates will adequately hydroxylate phenylalanine to the semiessential AA tyrosine. Objective: Our aim was to quantify human fetal phenylalanine and tyrosine metabolism. Design: Eight fasted, healthy, pregnant women undergoing elective cesarean delivery at term received primed continuous stable-isotope infusions of [1-C-13] phenylalanine and [ring-D-4] tyrosine starting before surgery. Umbilical blood flow was measured by ultrasound. Maternal and umbilical cord blood was collected and analyzed by gas chromatography-mass spectrometry for phenylalanine and tyrosine enrichments and concentrations. Data are expressed as medians (25th-75th percentile). Results: Women were in a catabolic state for which net fetal AA uptake was responsible for >= 25%. Maternal and fetal hydroxylation rates were 2.6 (2.2-2.9) and 7.5 (6.2-15.5) mu mol phenylalanine/(kg.h), respectively. Fetal protein synthesis rates were higher than breakdown rates: 92 (84-116) and 73 (68-87) lmol phenylalanine/(kg.h), respectively, which indicated an anabolic state. The median metabolized fraction of available phenylalanine and tyrosine in the fetuswas < 20% for both AAs. Conclusions: At term gestation, fetuses still show considerable net AA uptake and AA accretion [converted to tissue approximate to 12 g/(kg.d)]. The low metabolic uptake (AA usage) implies a very large nutritional reserve capacity of nutrients delivered through the umbilical cord. Fetuses at term are quite capable of hydroxylating phenylalanine to tyrosine. Am J Clin Nutr 2009; 89: 153-60.