Objective: To examine the effect of two lipid emulsions administered with total parenteral nutrition (TPN) on platelet aggregation and activation and the production of eicosanoids in nonseptic critically ill patients. Design: Prospective, randomized, unblinded, non-crossover study. Setting: ICU of a general teaching hospital. Patients: 23 adult, critically ill, nonseptic patients. who were in need of TPN for at least 7 days. Interventions: The patients were randomly distributed into 2 groups each of which received TPN with a different essential fatty acid content. The 2 lipid emulsions, Intralipid(R) 20% (long-chain triglycerides) and Lipofundin(R) MCT/LCT 20% (10% each of long- and medium-chain triglycerides) provided 43% of the nonprotein caloric requirements calculated for each patient. Parameters demonstrating platelet function (plasma beta-thromboglobulin, platelet factor 4, platelet aggregation, 6-keto-PGF(1 alpha)) were assessed before starting TPN and after 4 and 7 days of initiation. Results: Before beginning lipid perfusion, platelet activation evaluated by beta TG and PF4 levels was notable, 6-keto-PGF(1 alpha) production was elevated and no hyperaggregation of platelets was observed in patients. The studies of platelet function at 4 and 7 days of TPN did not show significant changes with respect to the basal data or between the 2 groups. Conclusion: Our results indicate that platelet function was not affected by either of the 2 lipid emulsions administered to patients during the study period.