Background: Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis. We assessed whether purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil have differential effects on platelet, fibrinolytic and vascular function in patients with both conditions. Methods: In a double-blind placebo-controlled trial of parallel design, 59 treated-hypertensive Type 2 diabetic men and postmenopausal women, were randomised to 4 g/day of EPA, DHA or olive oil (placebo) for 6 weeks. Collagen and PAF-stimulated platelet aggregation, collagen-stimulated thromboxane release (TXB2), plasma tPA and PAI-1 antigens, von Willebrand factor, p-selectin, and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery, were examined before and at the end of intervention. Results: Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study. Relative to placebo, DHA but not EPA supplementation significantly reduced collagen aggregation (16.9%, P = 0.05) and TXB2 (18.8%, P = 0.03). There were no significant changes in either PAF-stimulated platelet aggregation, fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo. Conclusion: Highly purified DHA may be a more effective anti-thrombotic agent than EPA. However, longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.