Background: The use of lipid emulsions has been associated with changes in lung function and gas exchange which may be mediated by biologically active metabolites derived from arachidonic acid. The type and quantity of the lipid emulsions used could modulate this response, which is mediated by the eicosanoids. This study investigates the use of omega-3 fatty acid-enriched lipid emulsions in ARDS patients and their effects on eicosanoid values. Methods. Prospective, randomized, double-blind, parallel group study carried out at the Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men; age: 58 13 years; APACHE II score 17.8 2.3; Lung Injury Score: 3.1 0.5; baseline PaO2/FiO2ratio: 149 40). Patients were randomized into two groups: Group A (n = 8) received the study emulsion Lipoplus 20%, B. Braun Medical (50% MCT, 40% LCT, 10% fish oil (FO)); Group B (n = 8) received the control emulsion Intralipid Fresenius Kabi (100% LCT). Lipid emulsions were administered for 12 h at a dose of 0.12 g/kg/h. We measured LTB4, TXB2, and 6-keto prostaglandin F 1values at baseline [immediately before the administration of the lipid emulsions (T-0)], at the end of the administration (T-12) and 24 hours after the beginning of the infusion (T 24) in arterial and mixed venous blood samples. Results: In group A (FO) LTB4, TXB2, 6-keto prostaglandin F1levels fell during omega-3 administration (T12). After discontinuation (T24), levels of inflammatory markers (both systemic and pulmonary) behaved erratically. In group B (LCT) all systemic and pulmonary mediators increased during lipid administration and returned to baseline levels after discontinuation, but the differences did not reach statistical significance. There was a clear interaction between the treatment in group A (fish oil) and changes in LTB4over time. Conclusions: Infusion of lipids enriched with omega-3 fatty acids produces significant short- term changes in eicosanoid values, which may be accompanied by an immunomodulatory effect. Trial registration. ISRCTN63673813. © 2011 Sabater et al; licensee BioMed Central Ltd.