Because glutamine is thought to be a major fuel for developing gut, we tested the hypothesis that extensive small-bowel resection alters whole-body glutamine metabolism in vivo. Eleven infants and children who had undergone extensive small intestinal resection (residual bowel length: 35 +/- 13 cm; mean +/- SD) and four control infants received 4-h primed, continuous i.v. infusions of L-[(1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state. The appearance rates of glutamine and leucine into plasma were determined from stable isotope enrichments in plasma at steady state. We observed the following: 1) Regardless of intestinal status, leucine and glutamine fluxes were higher in infants than values previously reported for adults. 2) Small-bowel resection was associated with a reduction in glutamine appearance rate (568 +/- 124 mumol.kg lean body mass-1.h-1 in short-bowel syndrome infants versus 816 +/- 149 mumol.kg lean body mass-1.h-1 in control infants; p < 0.05). 3) In contrast, leucine appearance rate was unaltered in short-bowel syndrome patients. The findings suggest that the small intestine plays a prominent role in glutamine metabolism in human infants.