The physiology of the interorgan exchange of amino acids in healthy subjects and in insulin-dependent diabetics is reviewed and compared with changes observed in patients with chronic renal failure. In contrast to the diabetic, who has elevated fasting branched-chain amino acid levels and diminished muscle uptake of branched-chain amino acid following protein feeding, fasting levels of leucine, isoleucine, and valine are decreased in uremia. Furthermore, the decline in branched-chain amino acids following insulin in normal and intracellular levels of leucine and isoleucine have been reported to be normal. With respect to alanine metabolism, the diabetic state is characterized by diminished fasting alanine levels which are due to a 2-fold increase in splanchnic alanine extraction. Accordingly, gluconeogenesis can potentially account for over 30 to 40% of hepatic glucose production compared to 15 to 20% in normal man. In uremia, fasting alanine levels are normal and hepatic alanine uptake is not increased. Similarly, basal hepatic glucose production, as well as suppression of glucose production following insulin, are normal in uremic subjects. Thus, although uremia is characterized by abnormalities in the metabolism of many individual amino acids, it does not appear to share the same disturbances in alanine and branched-chain amino acid metabolism that are associated with insulin deficiency.