Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia, who frequently exhibit endothelial dysfunction. The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population. Twenty-two healthy subjects (mean total cholesterol, 5.6 mmol/l) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and sterol esters, but low in saturated fat, or an ordinary Swedish diet, for 4 weeks in a randomized cross-over study. The composition of the diets were: in the Swedish diet, 2090 kcal (where 1 kcal=4.184 kJ; 48% of energy from carbohydrate, 15% from protein and 36% from fat) and 19 g of fibre; in the Mediterranean-inspired diet, 1869 kcal (48% of energy from carbohydrate, 16% from protein, 34% from fat) and 40 g of fibre. After each dietary period, fasting blood lipids, insulin and glucose levels, as well as apo B (apolipoprotein B) and LDL (low-density lipoprotein) particle size, were analysed. Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography, and arterial distensibility was assessed by echocardiography tracking. Fibrinolytic capacity across the forearm, as well as oxidative stress measured through urinary F(2)-isoprostane, were evaluated. Total, LDL- and apo B-cholesterol and triacylglycerol (triglyceride) concentrations were decreased by 17%, 22%, 16% and 17% respectively, after the Mediterranean-inspired diet compared with the Swedish diet ( P <0.05 for all). However, no differences in plasma concentrations of insulin and glucose and LDL particle size, endothelial function, arterial distensibility, fibrinolytic capacity or oxidative stress were detected. Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease. This beneficial effect was not mirrored in vascular function or oxidative stress evaluation.