BACKGROUND: Microembolic signals (MES) are associated with the pathogenic mechanism of ischemic stroke with large-artery atherosclerotic disease. We examined the relationship between MES on a transcranial Doppler ultrasonography (TCD) and lesion patterns on diffusion-weighted MR imaging (DWI) in acute ischemic strokes associated with atherosclerotic diseases of the middle cerebral artery (MCA) and internal carotid artery (ICA). METHODS: A total of 405 consecutive patients were monitored for MES within 48 hours of symptom onset. Patients with MES and DWI lesions in the territory of the MCA or ICA and corresponding MCA/ICA stenosis or occlusion on MR angiography (MRA) were included. MCA velocities and lesion patterns on DWI were compared. RESULTS: MES were detected in 25 patients (MCA: 13, ICA: 12). The mean number of MES during 30 minutes of monitoring was 14.2+/-17.3 (range: 1-64, MCA: 13.9+/-13.6, ICA: 14.5+/-21.6, p-value=0.098). The mean flow velocity in the ipsilateral MCA in patients with MCA disease was higher than in patients with ICA disease (129.9+/-74.4 cm/s vs 61.1+/-28.2 cm/s, p=0.006). The frequency of multiple lesions on DWI was higher inpatients with ICA disease than in those with MCA disease (46.1% vs 100%, p=0.003). CONCLUSIONS: Multiple lesions on DWI were more frequent in ICA disease with MES than in MCA disease. Artery-to-artery embolism may be a more important stroke mechanism in acute ischemic stroke with ICA disease.