The present studies investigated the effects of intravenous administration of the short-chain triglyceride triacetin on leucine metabolism in dogs. Animals received infusions of triacetin at 1.0 x estimated resting energy expenditure (REE), hyperenergetic triacetin at 1.5 x REE, glycerol, or saline during infusion of [1-14C]leucine. During both triacetin infusions, plasma alpha-ketoisocaproate concentrations increased (P < 0.05). During triacetin infusion at 1.5 REE, the plasma leucine concentration decreased (P < 0.05) and leucine rate of appearance decreased by approximately 19% (P < 0.05); this was significantly greater than the changes that occurred during triacetin at 1.0 x REE and glycerol (P < 0.05). There was no difference in leucine oxidation between the dogs given triacetin at 1.0 x REE and control groups, whereas leucine oxidation decreased by 53% during triacetin infusion at 1.5 x REE (P < 0.05). Nonoxidative leucine disappearance, an indicator of protein synthesis, did not change in any of the studies. These results indicate that triacetin has effects on leucine metabolism similar to those previously reported with long-chain triglyceride emulsions. Because of its water solubility, lack of toxicity, and favorable effects on protein metabolism, further studies are warranted regarding the use of triacetin as a parenteral nutrient.