Eicosapentaenoic acid (C20:5 omega 3), which is present in high concentration in certain salt-water fish, may reduce the incidence of cardiovascular disease in Greenland Eskimos by reducing platelet aggregation and adhesion. Changes in platelet and plasma fatty acids, platelet aggregation, and thromboxane (TX) formation were studied in 7 healthy White men who had been on a mackerel diet for 1 week. Platelet aggregation had TX synthesis after low-dose collagen stimulation in platelet-rich plasma were reduced. This could be due to the marked change of the ratio of C20:5 to arachidonic acid (C20:4 omega 6) in platelet membranes. When the men were on the mackerel diet, their C20:5 level in platelet membranes and in plasma increased and that of C20:4 dropped. Both fatty acids were released during platelet aggregation. The reduction in the amount of C20:4 liberated and/or a diminished conversion of C20:4 to TXA2 by competitive inhibition of the platelet cyclo-oxygenase by the released C20:5 could be responsible for the decreased platelet aggregation.