Histological abnormalities of the atherosclerotic lesion are closely related to the stability of the plaque. Specifically, the plaque is likely to be unstable if the fibrous cap is thin. However, ultrasonic characterization of the atherosclerotic lesion has not been done from this viewpoint. Thus, in the present study ultrasonic tissue characterization of the carotid atherosclerotic lesion was attempted to assess the stability of the plaque. Integrated ultrasonic backscatter (IBS) in the atherosclerotic lesion was compared with histological findings of the respective tissue in 35 patients with carotid artery stenosis who underwent carotid endarterectomy. Carotid IBS was determined by locating the region-of-interest (ROI) in the center of the atherosclerotic lesion and calibrating by subtracting the IBS in the tunica externa of the vessel from the IBS of the ROI. IBS was also determined at the interface of the plaque, and at this site it was analyzed in relation to the thickness of the fibrous cap. Lipid content, fibrous tissue, thrombus, hemorrhage and calcification were histologically assessed in the respective tissue. Carotid IBS in the lipid lesion (-22.5+/-4.1 dB) was significantly different from that of fibrous, hemorrhagic or calcified lesions (-11.1+/-7.1, -27.5+/-4.1, +2.1+/-6.5 dB, respectively), but there was no significant difference in IBS between the lipid lesion and thrombus (-15.2+/-8.8 dB). IBS was lower in the thin fibrous cap than in the thick lesion (-10.9+/-6.4 vs -2.4+/-6.2 dB, p<0.001). IBS can be used to characterize atherosclerotic lesions in the carotid artery; a low value at the interface suggests a thin fibrous cap, which is frequently associated with unstable plaque.