Physiological and pathophysiological reactions like vascular resistance, thrombosis, wound healing, inflammation and allergy are modulated by oxygenated metabolites of arachidonic acid and related polyunsaturated fatty acids that are collectively termed eicosanoids. These compounds include prostaglandins, prostacyclin, thromboxane, leukotrienes and hydroxylated derivatives of arachidonic acid. The eicosanoids are all derived from essential fatty acids that must be provided in the diet, 4 and production of eicosanoids is controlled by cellular mechanisms for the uptake, release and oxygenation of the eicosanoid precursor fatty acids. Interference with eicosanoid synthesis is characteristic of many of the therapeutic agents in use in developed countries, including anti-inflammatory drugs and antithrombotic agents, antihypertensives and diuretics, suggesting that eicosanoids are involved in a broad spectrum of disease processes prevailing in these countries. A change of eicosanoid production and eicosanoid-dependent cellular functions may, however, also be achieved by altering eicosanoid precursor availability. Under our Western dietary conditions, arachidonic acid (AA; 20:4n6) is by far the dominant precursor fatty acid of biologically highly active eicosanoids of the two series. The major primary source of AA in our food chain is linoleic acid (18:2n6). At variance to the fatty acids of the linoleicor n 6-family in terrestrial animals and in most plant seeds---which are the major sources of our eicosanoid precursor fatty acids--the fatty acids of the linolenicor n 3-family predominate in green leaves and especially in marine lipidsY Here, eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) are the major polyunsaturated fatty acids. Several independent lines of evidence suggest that changes in the natural history of hypertensive, atherothrombotic and inflammatory disorders may be achieved by altering the eicosanoid precursor availability. Native Greenland Eskimos 6 and also Japanese ~2 have a high dietary intake of long chain n 3 polyunsaturated fatty acids from seafood and a low incidence of myocardial infarction. Diets containing n 3 polyunsaturated fatty acids have also been found to reduce the severity of experimental cerebral 2 and myocardial S infarction, and retard autoimmune nephritis and prolong survival in NZB x NZW FI mice. m6 The eicosanoids derived from eicosapentaenoic acid have a spectrum of biological activity that is desirably different from that of the eicosanoids derived from arachidonic acid. However, until now, formation of eicosanoids from eicosapentaenoic acid has only been found in in vitro experiments.