Long-chain triglycerides (LCTs) contained in total parenteral nutrition (TPN) regimens provide a considerable energy substrate in malnourished patients. Their effect on the immune system is controversial, however. In this randomized, prospective study we investigated the possible differences between the effect of TPN with LCTs or medium-chain triglycerides (MCTs) on T-lymphocyte subpopulations. Our study included 15 normal subjects, 20 patients receiving glucose-based TPN, and 40 patients receiving glucose-fat-based TPN. In the last group 20 patients received TPN that included LCTs and 20 received 50% MCTs and 50% LCTs. T-lymphocyte subpopulations, including total T cells and T-helper, T-suppressor, and NK cells, as well as the ratio of helper to suppressor T cells were determined before and 10 d after initiation of TPN. We found a significant decrease in the ratio of helper to suppressor T cells in the LCT group although no such difference was detected in the MCT-LCT group. No difference whatever was found in total T cells and helper, suppressor, and NK cells.