Much of the interest in amino acid metabolism has centered on the intermediary steps involved in catabolism, the regulation of biosynthesis and transport, and genetic disorders resulting in abnormal urinary and/or plasma concentrations of amino acids. This review will focus on recent studies in which amino acid exchange between various organs has been examined in a variety of physiologic and pathologic conditions in intact humans. Particular emphasis, reflecting my own interest, will be focused on the relationship of amino acid metabolism to gluconeogenesis, its interaction with glucoregulatory hormones, and its role in nitrogen exchange. The technique used in determining tissue exchange of amino acids in many of the studies to be reviewed involves simultaneous sampling of arterial and venous blood across various organs and measuring blood flow. Where applicable, reference will be made to studies in experimental animals, although the data in humans form the overall basis of this review.