Hypermetabolism with negative nitrogen balance and immune deficiencies characterize the systemic response to major thermal injury. Patients with burns greater than 50% of the total body surface area (TBSA) initially have poor gastrointestinal function, making it difficult to deliver sufficient enteral calories to meet nutritional requirements. Controversy has developed over whether to supplement oral alimentation with total parenteral nutrition (TPN) early in their treatment. This study randomly assigned 28 patients with burns greater than 50% TBSA to receive TPN supplementation or no TPN supplementation in the first 10 days postburn. Patients receiving TPN supplementation had significantly lower T-cell helper-to-suppressor cell ratios than the unsupplemented group. However, there was no difference in mortality between the groups (eight in each). All patients who died developed hepatomegaly associated with fatty infiltration cholestasis and antemortem liver function abnormalities, indicating that this syndrome is the result of burn injury itself, not TPN.