One important advantage of animal models is that they permit invasive approaches and can be especially valuable when evaluating tissue and specific features of metabolism in situ. The focus of this presentation is current models, which are providing insights into the pivotal importance of the gastrointestinal tract in amino acid metabolism. Intestinal amino acid metabolism is conceptually and technically difficult to approach and multiple processes must be accounted for: protein synthesis and degradation; transit of amino acids in both directions across the basolateral surface of enterocytes, in addition to uptake on the apical side; arterio-portal differences as well as net portal appearance during uptake of defined amino acid mixtures appearing on the luminal side; first pass amino acid metabolism. These key features are largely impossible to study without access to invasive approaches in vivo and cannot be reproduced in vitro. Douglas Burrin, Ron Ball, and Vickie Baracos and their co-workers have used the domestic piglet to study intestinal protein metabolism in situ in three distinctly different and complementary approaches. Collectively, their approaches allow a means to describe the key elements of intestinal amino acid capture (and release) and the means to probe their physiological and pathological variation. It seems evident that the portal-drained viscera represent sites of quantitatively important amino acid catabolism, and that this capacity combined with hepatic metabolism would largely limit the possibility of toxic sequelae of amino acids taken orally.