It remains a significant technical challenge for duplex ultrasound to accurately differentiate between total and near total internal carotid artery (ICA) occlusions. We have evaluated the efficacy of an ultrasound contrast agent combined with improved imaging techniques in patients with suspected carotid artery occlusions. Patients identified by conventional duplex ultrasound between January and August 2003 as having a possible ICA occlusion were eligible for study. A 1 mL bolus of ultrasound contrast agent was injected into a 50 mL bag of normal saline and given intravenously at a rate of approximately 4-5 mL/minute. Ultrasound imaging and spectral Doppler analysis were done using tissue harmonic imaging for optimum contrast agent to soft tissue discrimination, or with the direct B-mode imaging of blood flow to maximize the brightness of the circulating contrast agent. Ten patients were identified, 6 men and four women with a mean age of 68.3 years. Nine suspected total ICA occlusions were unilateral and 1 was bilateral. Imaging with contrast agent confirmed occlusion of the ICA in 7 of 10 patients; 3 patients had near-total occlusion with flow detected in the distal ICA by spectral and color Doppler. All 3 of these near-total occlusions were ultimately confirmed by either conventional or magnetic resonance carotid angiography. The contrast agent was most beneficial in improving the detection of minimal flow beyond a severe stenosis and in evaluating flow dynamics in the presence of severely calcified plaque. We conclude that the use of an ultrasound contrast agent with newer duplex ultrasound imaging techniques can reliably distinguish total from near-total internal carotid artery occlusions. Future prospective studies should be able to define the efficacy of ultrasound contrast agents in improving the overall diagnostic accuracy of duplex ultrasound in technically difficult cases and in patients with complex peripheral vascular disease.