Feeding sesamin and alpha-tocopherol in combination, both at the 0.5% dietary level, to Sprague-Dawley rats for 3 weeks resulted in a trend toward decreasing the proportion of 20:4n-6 and 22:5n-6 and increasing that of 18:2n-6 in phosphatidylcholine from various tissues, suggesting interference with the metabolism of linoleic acid. This dietary manipulation significantly reduced the production of leukotriene C4 in the lung, the splenic production of leukotriene B4, and reduction of the plasma histamine level. Simultaneous administration of sesamin and alpha-tocopherol significantly increased the production of IgA, IgG, and IgM by mesenteric lymph node lymphocytes, while the IgE level tended to be reduced. These effects were not necessarily apparent by feeding these compounds separately. Thus, sesamin and alpha-tocopherol in combination would be effective for regulating the eicosanoid production and modifying the immune function.