Omega-3 ( É÷ 3) fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular disease. Despite these benefi ts, concern remains that É÷ 3 fatty acids may increase lipid peroxidation. It has previously been shown that urinary F 2 -isoprostanes (F 2 -IsoPs) were reduced following É÷ 3 fatty acid supplementation in humans. It is now determined whether EPA or DHA supplementation affects plasma F 2 -IsoPs. In two 6-week placebo-controlled interventions, Study A: overweight, dyslipidaemic men; and Study B: treated-hypertensive Type 2 diabetic, patients were randomized to 4 g daily EPA, DHA. Post-intervention plasma F 2 -IsoPs were signifi cantly reduced by EPA (24% in Study A,19% in Study B) and by DHA (14% in Study A, 23% in Study B) relative to the olive oil group. The fall in plasma F 2 -IsoPs was not altered in analyses that corrected for changes in plasma arachidonic acid, which was reduced with EPA and DHA supplementation. Neither F 3 - nor F 4 -IsoPs were observed in plasma in both studies. These results show that in humans, EPA and DHA reduce in vivo oxidant stress as measured in human plasma and urine. ===========================