BACKGROUND Elevated levels of soluble adhesion molecules are found in subjects with vascular disease and inconsistently in subjects with conditions predisposing them to atherosclerosis, such as hypercholesterolaemia and diabetes. Oxidized low-density lipoprotein (LDL), protein kinase C and lower than normal levels of NO appear to be important for expression of adhesion molecules, raising the possibility that vitamin E is useful for downregulating levels. We have recently shown that administration of 1000 IU vitamin E for 3 months will improve endothelial vasodilator function (EVF) in uncomplicated type-1 diabetes. OBJECTIVE To determine whether levels of soluble adhesion molecules in young subjects with uncomplicated diabetes are elevated, whether there is a relationship between levels of soluble adhesion molecule and EVF as well as parameters of diabetes and lipid levels and whether an improvement in EVF related to vitamin E therapy is also associated with a decrease in levels of soluble adhesion molecules. DESIGN A randomized, placebo-controlled, study. RESULTS There was no difference between levels of soluble vascular cell adhesion molecule-1 (VCAM-1; 621 +/- 17 versus 635 +/- 37 ng/ml) and P-selectin (59 +/- 2 versus 57 +/- 6 ng/ml) for the diabetic and control groups. For the diabetic cohort, levels of soluble VCAM-1 were inversely related to flow-mediated vasodilatation of the brachial artery (r = -0.41, P < 0.005) and directly related to levels of total cholesterol (r = 0.44, P < 0.005) and LDL cholesterol (r = 0.42, P < 0.01) and duration of diabetes (r = 0.55, P < 0.0005) but there was no relationship with susceptibility of LDL to oxidation or vitamin-E content of LDL. Levels of soluble P-selectin were directly related to duration of diabetes (r = 0.43, P < 0.05) and inversely related to size of LDL particles (r = 0.32, P < 0.05) but were not related to EVF. Vitamin E produced no change in levels of soluble P-selectin and VCAM-1. CONCLUSIONS Levels of soluble VCAM-1 and P-selectin in young subjects with type-1 diabetes and no evidence of overt vascular disease do not appear to be elevated and are not influenced by vitamin-E supplementation.