We have reported that infusion of trioctanoin in conscious dogs had little effect on leucine oxidation but decreased the rate of appearance (Ra) and interconversion of leucine and its alpha-keto acid, alpha-ketoisocaproate (KIC). To verify that these conclusions were independent of the leucine tracers and isotope models employed, the studies were repeated using [1-14C]leucine and [4,5-3H]KIC rather than [1-14C]KIC and [4,5-3H]leucine. In the present study, leucine oxidation calculated using the plasma [14C]leucine or [14C]KIC specific activities (SA) increased nearly twofold (P less than 0.001) during trioctanoin infusion in direct contrast to our previous results. When the data from either study were analyzed using the plasma SA of the leucine moiety reciprocal to the infused tracer as a potential indicator of the intracellular leucine SA, similar conclusions were obtained from either study: trioctanoin infusion in conscious dogs appears to increase whole-body leucine oxidation and does not decrease proteolysis. These studies challenge the validity of previously used isotope models of leucine metabolism and suggest that the plasma KIC SA during infusion of labeled leucine may most accurately reflect changes in whole-body leucine metabolism.