To determine the hydrolysis rate of medium-chain triglycerides (MCTs) to medium-chain free fatty acids (MCFAs) and the disposition rate of MCFAs, five healthy volunteers (H) and eight surgically stressed patients (S) received 0.5 mL of Lipofundin 20% per kilogram body weight as an intravenous bolus. Serum MCTs (C8 and C10) and MCFAs were measured by high-performance liquid chromatography during the 120 minutes postinjection. A linear two-compartment model was found to be descriptive and robust: the apparent volumes of distribution were found to be similar in healthy and surgical subjects for both MCTs and MCFAs. The first-order transformation rate constant (hydrolysis) from MCTs to MCFAs was not significantly different between the H and S groups (overall 0.112 +/- 0.022/min, C8; 0.078 +/- 0.020/min, C10). The rate constant for tissue MCFA uptake from plasma was significantly different between S and H subjects both for C10 alone (H: 0.0337 +/- 0.0078; S: 0.1194 +/- 0.0240; p = .020) and for C8 and C10 together (H: 0.0382 +/- 0.0054; S: 0.1012 +/- 0.0168; p = .008), whereas it failed to attain significance when C8 alone was considered (H: 0.047 +/- 0.0077; S: 0.0829 +/- 0.0230; p = .210). These results show that use of MCTs is increased in surgical patients because of enhanced tissue uptake of the corresponding free fatty acids, whereas there does not seem to be an increase of MCT hydrolysis in response to acute disease. This would indicate that the stressed patient is in fact able to effectively use this alternative lipid substrate in the face of increased metabolic demand.