Amino acids are essential nutrients for living organisms. There are genetic differences in voluntary consumption of amino acids among mouse strains. In two-bottle preference tests, C57BL/6ByJ (B6) mice consume more glutamate (Glu) and glycine (Gly) solutions than do 129P3/J (129) mice. To examine the role of postingestive metabolism of these amino acids in regulation of their intake, we compared metabolism of orally administered Glu and Gly in B6 and 129 mice. After administration of Glu, there were increases in circulating glucose and insulin in B6 mice, whereas 129 mice had elevated blood alanine and body temperature. After ingestion of Gly, B6 mice had increases in blood glucose, whereas there was an elevation of body temperature in 129 mice. These data suggest that B6 mice preferably convert ingested Glu and Gly to glucose in contrast to 129 mice, which preferably use them for thermogenesis. This study strongly supports the hypothesis that the metabolic fate of a nutrient plays an important regulatory role in control of its intake. This is the first detailed study of mouse strain differences in amino acid metabolism.