Nutrient-induced thermogenesis (NIT) after parenteral administration of amino acids (AAs) was investigated in rats and compared with result obtained with intragastric administration. Resting energy expenditure was measured with a new type of open-circuit indirect calorimeter. The NIT increased shortly after parenteral AAs administration and reached a steady state in 30 minutes. The change in resting energy expenditure (the increment of resting energy expenditure over preinfusion baseline values) showed a significant relationship not only with the amount of infused AAs but also with the AA concentration in the portal vein. Furthermore, the increase in plasma AA concentrations in the portal vein was proportional to the amount of the particular AA infused. This relationship held true over the entire range tested. NIT with parenteral infusion (11% to 12%) was lower than that with intragastric infusion (20% to 23%). Plasma insulin, corticosterone, and glucagon levels increased after both parenteral and intragastric AAs administration, but the two methods did not show any significant differences in hormonal changes. The plasma aminogram of the portal vein after intragastric infusion was compared with that after parenteral infusion. Total plasma AA concentration and the levels of glutamine, lysine, arginine, glutamate, aspartate, and histidine were lower but the level of isoleucine was higher after intragastric infusion. On the basis of these results, it is believed that parenteral administration of AAs can induce thermogenesis, which may be regulated by the intraportal AA concentration. Considering the remarkable decrease in glutamine in the portal vein after intragastric infusion, the cost of intestinal metabolism may predominantly contribute to the NIT resulting from intragastric infusion.