Although the lung is known to be a major producer of glutamine and contributes to glutamine homeostasis, little is known about glutamine during development. We hypothesize that glutamine synthetase (GS) undergoes changes in activity and steady state mRNA from infancy to adulthood. GS activity and RNA were measured in the lungs of rat term fetuses, 5, 10, and 19-day-old infants, and adults following treatment with saline (SAL) or 0.2 mg/kg dexamethasone (DEX). Significant interactions between treatment and age effects were noted for both mRNA and specific activity indicating that the degree of difference between SAL and DEX treatment groups depended on age (2 way ANOVA). Pairwise comparisons indicate that mRNA quantity and specific activity were greater in the 5-day DEX group. Within the SAL treatment set, mRNA levels did not differ among age groups; however, specific activity of the 19-day group was greater than fetal, 5-day and 10-day specific activities. Within the DEX treatment set, the mean mRNA level of the 5-day group was greater than in the other age groups; however, DEX treatment did not alter the specific activities among age groups. Immunohistochemical analysis demonstrates that GS enzyme is located primarily in the smooth muscle layer of the pulmonary vasculature. These data demonstrate that: 1) GS responds to exogenous glucocorticoids prior to the endogenous glucocorticoid surge; and 2) the effects of glucocorticoid treatment are blunted when endogenous glucocorticoids are elevated. Our data suggest that: 1) glucocorticoid receptors are unavailable to exogenous glucocorticoids when endogenous glucocorticoids are elevated; and 2) localization of GS in the pulmonary smooth muscle layer permits rapid release of glutamine into the circulation during periods of high glutamine demand. Supported by NIH Grant#RO1-HD29279.