The effects of a short-term (5 days) continuous intragastric tube feeding of diets containing n - 6 polyunsaturated fatty acids (PUFA) from safflower oil (SO) or n - 3 PUFA from menhaden oil (MO) on the production of proinflammatory mediators, and on the number of animals surviving after an intravenous injection of lipopolysaccharide (LPS) were investigated in rats. The phospholipid fatty acid composition of cell membranes from several organs and of plasma were also analyzed. No marked differences in the number of animals surviving or in the production of tumor necrosis factor-alpha were observed between the 2 groups of animals. However, 90 min after LPS exposure the plasma levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha decreased significantly (40% and 60%, respectively) for the group of rats fed MO diet compared to those fed SO diet (P < 0.05). Following continuous infusion of liquid MO diet, the amount of arachidonic acid (AA) detected was significantly lower in plasma (23%), spleen (43%), lungs (41%), and liver (38%), but was unchanged in the heart tissues. The percent of eicosapentaenoic acid (EPA) incorporated into phospholipids of plasma, spleen, lungs, liver, and heart were 7.6, 4.4, 2.1, 7.2, and 1.1%, respectively. These data indicate that after continuous MO feeding, a significant decrease in the production of proinflammatory eicosanoids was associated with a marked reduction in AA content. Further, these data suggest that nutritional intervention may have a therapeutic potential to ameliorate clinical symptoms due to excessive productions of eicosanoids during acute septic complications.