This study was performed to determine whether hypercholesterolemic men had increased large artery intima-media thickness (IMT), a potential surrogate measure of atherosclerosis, compared to normocholesterolemic controls. The measurements were performed in the far walls of common carotid and femoral arteries with non-invasive automatic computerized ultrasonic technique in 101 asymptomatic men (28-60 years) of whom 40 were normocholesterolemic (total cholesterol < 5.2 mmol/l, controls), 25 had borderline hypercholesterolemia (5.2 < or = total cholesterol < 6.2 mmol/l, group 1) and 36 had hypercholesterolemia (total cholesterol > or = 6.2 mmol/l, group 2). All the subjects had no other traditional risk factors, except smoking. Carotid and femoral IMT were significantly increased in group 2 (P < 0.01) but not in group 1 compared to controls. When all subjects were pooled for analysis, carotid and femoral IMT were correlated (r = 0.47, P < 0.001) and increased with total cholesterol (r = 0.35, P < 0.001) and LDL cholesterol (r = 0.33, r = 0.34, respectively; P < 0.001). Carotid and femoral IMT increased with age in each group: controls, r = 0.46, P < 0.01 and r = 0.50, P < 0.001, respectively; group 1, r = 0.42, P < 0.05; group 2, r = 0.48, P < 0.01, and r = 0.59, P < 0.001, respectively. At the carotid and femoral sites, the regression slopes between age and IMT were steeper in group 2 than in controls (P < 0.01). Thus, hypercholesterolemia was associated with diffuse large artery wall thickening, whose presence might be useful in the identification of those hypercholesterolemic individuals most prone to developing atheromatous changes, in the decision to treat, and in the monitoring of lipid-lowering treatment.