Endothelial dysfunction is considered a key early event in atherosclerosis. Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and compared to that in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5% vs 9%, (p = 0.0002) and 14% vs 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The maximum albumin excretion rate of the diabetic group was 17 micrograms/min. Four adolescents had retinopathy assessed by stereoscopic fundus photography. Three had at least one of four cardiovascular autonomic test abnormalities. There was no significant correlation observed between the test for early large vessel disease and those for diabetic microangiopathy. Large vessel dysfunction was the most common abnormality.