The purpose of this study was to assess the effects of addition of L-glutamine to an IV nutritional solution on the urinary excretion of 3-methylhistidine (3-MeH) and the morphology of the musculature of the gut in rats. Two experiments were run. In experiment 1 glutamine was added to a mildly hypocaloric IV solution which contained no other amino acids. For experiment 2 glutamine was added to an isocaloric balanced amino acid mixture. In both experiments L-alanine was added in equimolar amounts in place of the L-glutamine for the control groups. Providing glutamine in an IV diet without other amino acids significantly decreased urinary 3-MeH excretion (p less than 0.05). Electron microscopy and morphometric analysis of the jejunum showed an approximate 50% loss of musculature from the gut wall in alanine-treated animals. Glutamine supplementation of a balanced amino acid regime had no effect on urinary 3-MeH excretion or the musculature of the jejunum. We concluded that (1) glutamine is a preferred fuel for jejunal smooth muscle as well as for mucosal cells of the jejunum and (2) only when amino acids are limiting does exogenous glutamine prevent atrophy of the gut musculature.