1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits, We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease, 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean+/-SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E 400 i.u, daily, (n=10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mu mol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group, Lipid profiles remained similar before and after supplementation in both groups, Forearm blood how responses to acetylcholine (7.5 and 15 mu g/min) and nitroprusside (3 and 10 mu g/min) were similar before and after supplementation in both groups, Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 mu g/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.