To investigate the effects of fasting and postprandial glucose on endothelial cell function and intima-media thickness, we studied 60 men with cardiovascular risk factors. Postischemic, endothelium-dependent vasodilatation was measured after 3 minutes of ischemia at the radial artery with high-resolution echo tracking. Common carotid artery intima-media thickness was measured by B-mode ultrasound. Glucose tolerance was determined by a 75-g oral glucose load. Fasting glucose levels were inversely correlated with postischemic, endothelium-dependent vasodilatation (r=-0.24, P<0.05) and directly correlated with intima-media thickness (r=0.26, P<0.05). However, postischemic, endothelium-dependent vasodilatation and intima-media thickness were not correlated. All subjects with normal postischemic, endothelium-dependent vasodilatation also had a normal intima-media thickness, whereas some subjects with impaired postischemic, endothelium-dependent vasodilatation also had a normal intima-media thickness. Multiple regression analysis revealed a profound influence of age on intima-media thickness to the exclusion of all other variables. The same age-adjusted analysis for postischemic, endothelium-dependent vasodilatation accepted fasting glucose, followed by 2-hour postprandial glucose, as variables, but no others. Subjects with fasting glucose values >100 mg/dL showed reduced postischemic, endothelium-dependent vasodilatation (59 versus 120 microm, P<0.05) and a higher intima-media thickness (right: 0.76 versus 0.62 mm, P<0.05; left: 0.78 versus 0.63 mm, P<0. 05) compared with those with fasting glucose values <100 mg/dL. Subjects with 2-hour postprandial glucose values >125 mg/dL had no reduced postischemic, endothelium-dependent vasodilatation compared with subjects with a 2-hour postprandial glucose <125 mg/dL; however, their intima-media thickness (right: 0.66 versus 0.62 mm; left: 0. 68 versus 0.62 mm; P<0.05 for both) was greater. Thus, high fasting rather than postprandial glucose values are associated with both postischemic, endothelium-dependent vasodilatation and increased intima-media thickness. Postischemic endothelium-dependent vasodilatation may precede increased intima-media thickness.