Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28 -30 wk; birth weight, 820 -1610 g) receiving parenteral nutrition supplying 1.5 g · kg Ϫ1 · d Ϫ1 amino acids and approximately 60 nonprotein kcal · kg Ϫ1 · d Ϫ1 were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g · kg Ϫ1 · d Ϫ1 ; glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH 13 CO 3 to assess the recovery of 13 C in breath, immediately followed by a 3-h L-[1-13 C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 Ϯ 94 versus 503 Ϯ 83 M, mean Ϯ SD; p Ͻ 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (Ϫ16%, p Ͻ 0.05) and leucine oxidation (Ϫ35%, p Ͻ 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (Ϫ20%, p Ͻ 0.05), and 4) no change in protein balance (nonoxidative leucine disposal Ϫ leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants. During the last decade, several clinical trials have produced compelling evidence for a role of glutamine in improving nitrogen balance in adult patients undergoing elective gastrointestinal surgery (1, 2), cholecystectomy (3), or bone marrow transplantation (4). Other studies suggested glutamine might exert a trophic effect on gut as well (5-7).Although preterm infants are exposed to stress-induced protein wasting and intestinal frailty, conventional amino acid solutions designed for neonatal i.v. nutrition do not contain glutamine, because glutamine is classified as nonessential, has relatively poor solubility, and cannot be heat sterilized. Yet Neu et al. (8)