The intestinal tract plays a central role in the protein catabolic response after injury and infection. The mucosa utilizes glutamine and thus spares glucose--presumably sparing this essential fuel source for tissues with an obligate glucose requirement. With inadequate nutritional support or prolonged stress, glutamine levels decrease in both the plasma and the tissue pools, which suggests that glutamine deficiency occurs. This is associated in time with atrophy of the gastrointestinal mucosa. This provision of dietary glutamine results in correction of the abnormally low glutamine concentrations and increased cellularity of the gut mucosa. The derangements in the intestinal mucosa associated with starvation, injury, infection, immunosuppression, chemotherapy, lack of enteral feedings, and other stresses are associated with a breakdown in the barrier function of the gut. Both bacteria and their toxins may enter the host from the intestinal lumen. Through interaction with the reticuloendothelial system, cytokines are produced, which stimulate the pituitary-adrenal axis and thus contribute to the stress response. The elaboration of glucocorticoids facilitates proteolysis, thus increasing glutamine release from skeletal muscle for gut repair. Although this homeostatic mechanism appears to aid mucosal repair and support immunologic responses, severe injury or prolonged glutamine deficits do not adequately support intestinal recovery and allow this cycle to become self-perpetuating (Fig 3). Adequate enteral feedings initiated early in the course of a disease appear to maintain adequate gut barrier function. In the frequent circumstance when feeding by this route is inadequate or impossible, glutamine-containing parenteral feedings offer an appropriate alternative therapy for bowel and immunologic support. Glutamine-containing parenteral feedings are associated with increased mucosal cellularity and improved survival after gut injury. Specific hormones also stimulate mucosal growth, and it is anticipated that a combination of hormones and specific nutrients will provide optimal support of the gut mucosa in the severely ill patient.