Objective: To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Design: Prospective, sequential investigation comparing three different FO doses. Subjects: Three groups of male subjects aged 26.8 ± 3.2 years (BMI 22.5 ± 2.1). Intervention: One of three FO doses (Omegaven Ò 10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS, 0.2 g/kg 1 day before, or 0.2 g/kg 2 h before. Measurements and results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-a, stress hormones) were collected. After LPS temperature, ACTH and TNF-a concentrations increased in the three groups: the responses were significantly blunted (p \ 0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-a and temperature AUC values were observed after a single 0.2 g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent. Conclusions: Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects.