This study was conducted to determine the effects of arachidonic acid (AA) supplementation on human immune response (IR) and on the secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Ten healthy men (20-38 yr) participated in the study and lived at the Metabolic Suite of the Western Human Nutrition Research Center. They were fed a basal diet (57, 27, and 16 energy percentage from carbohydrate, fat, and protein, respectively, and AA 200 mg/d) for the first 15 d of the study. Additional AA (1.5 g/d) was added to the diet of six men from day 16 to 65, while the remaining four subjects remained on the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indices of IR were examined using blood drawn on days 15, 58, 65, 108, and 115. Influenza antibody titers were determined in the sera prepared from blood drawn on days 92 and 115 (23 d postimmunization). AA supplementation caused significant increases in the in vitro secretion of LTB4, and PGE2, but it did not alter the in vitro secretion of tumor necrosis factor alpha; interleukins 1 beta, 2, 6; and the receptor for interleukin 2. Nor did it change the number of circulating lymphocytes bearing markers for specific subsets (B, T, helper, suppressor, natural killer) and the serum antibody titers against influenza vaccine. The opposing effects of PGE2 and LTB4 may have led to the lack of change in immune functions tested.