The changes in fatty acid composition in phospholipids of guinea-pig lung parenchymal strips and trachea induced by dietary administration of eicosapentaenoic acid (EPA) were investigated as well as the resultant changes in leukotriene (LT) C4- and D4-induced contractions of guinea-pig tracheal smooth muscle. EPA levels in both parenchymal strips and trachea were significantly increased depending on the administered dose of EPA, but on the other hand, arachidonic acid levels in those preparations were not changed. Both the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 were significantly reduced in the EPA-treated group compared with the control group at all 3 concentrations, 10(-9), 3 x 10(-9) and 10(-8) mol/l, in the presence of 5 x 10(-5) mol/l indometacin, a cyclooxygenase inhibitor. But this significant reduction of the contraction was not recognized between these 2 groups in the presence of 10(-5) mol/l 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, or in the combined presence of 5 x 10(-5) mol/l indometacin and 10(-5) mol/l of AA861. These results suggest that: 1. a 5-lipoxygenase pathway is partly involved in the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 and; 2. EPA suppresses LTC4- and D4-induced contractions of guinea-pig tracheal smooth muscle through a 5-lipoxygenase pathway.