Eight nutritionally depleted and five injured patients were studied prior to and during total parenteral nutrition (TPN). Five additional injured patients were studied at intervals while receiving only 5% dextrose. Fatty acid kinetics and oxidation were determined using an infusion of [1-14C]palmitate. Net substrate oxidation was calculated by indirect calorimetry. During TPN, resting energy expenditure rose from 109 to 119% and from 89 to 103% of predicted in injured and depleted patients, respectively. Free fatty acid (FFA) flux was unaffected, FFA oxidation and net fat oxidation (NFO) decreased by 60%. However NFO began higher in injured subjects (20.7 +/- 2.8 vs 14.6 +/- 0.9 kcal/kg/day, P less than 0.05) and remained higher during TPN (8.3 +/- 1.2 vs 5.6 +/- 0.9 kcal/kg/day, P less than 0.05). The proportion of NFO derived from immediate oxidation of circulating FFA was approximately 35%. The results indicate that, with glucose-based TPN, there is a discrepancy between suppression of FFA production and oxidation. We further conclude that sources of fatty acid which are not in rapid equilibrium with circulating plasma FFA contribute substantially to whole body fat oxidation.