Vascular cell adhesion molecule-1 (VCAM-1) has been shown to be highly expressed in atherosclerotic lesions. Although the soluble form of VCAM-1 (sVCAM-1) is detected in human sera, the relation between the degree of atherosclerosis and serum sVCAM-1 level has not been defined. In the present study, sVCAM-1 concentrations were measured in sera from 101 Japanese NIDDM patients. The mean +/- SD serum sVCAM-1 concentration in 26 patients with symptomatic atherosclerotic vascular diseases (789 +/- 187 ng/ml) was higher than that in 75 patients without the disease (664 +/- 175 ng/ml). Among the 101 NIDDM patients, 56 had atherosclerotic change of the carotid arteries, based on the evaluation by high-resolution B-mode ultrasonography. Their sVCAM-1 level was 759 +/- 201 ng/ml, higher than that in 45 patients without any detectable atherosclerosis of the carotid arteries (619 +/- 130 ng/ml). In addition, there was a positive correlation between sVCAM-1 concentration and thickness of the intimal plus medial complex (IMT) of the carotid arteries in the NIDDM patients (r = 0.41, P < 0.0001). Multivariate regression analysis revealed significant predictors of mean IMT value to be sVCAM-1 concentration (F = 62.88, P = 0.0001) and age (F = 9.59, P = 0.0026). By contrast, sVCAM-1 concentration was not increased in nondiabetic patients with atherosclerotic change of the carotid arteries (668 +/- 191 ng/ml; n = 36) compared with those without the atherosclerotic change (632 +/- 177 ng/ml; n = 28), and there was no correlation between sVCAM-1 level and IMT of the carotid arteries in the nondiabetic subjects. These results indicate that circulating sVCAM-1 may be a marker of atherosclerotic lesions in NIDDM patients with symptomatic and asymptomatic atherosclerosis.