Superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. The diagnostic yield of transesophageal and transthoracic echocardiography for identifying a cardiac source of embolism was compared in 79 patients presenting with unexplained stroke or transient ischemic attack. There were 35 men and 44 women with a mean age of 59 years (range 17 to 84); 52% had clinical cardiac disease. Both transthoracic and transesophageal echocardiograms were performed using Doppler color flow and contrast imaging. Transesophageal echocardiography identified a potential cardiac source of embolism in 57% of the overall study group compared with only 15% by transthoracic echocardiography (p less than 0.0005). Compared with transthoracic echocardiography, transesophageal echocardiography more frequently identified atrial septal aneurysm associated with a patent foramen ovale (9 versus 1 of 79 patients, p less than 0.005), left atrial thrombus or tumor (6 versus 0 of 79 patients, p less than 0.05) and left atrial spontaneous contrast (13 versus 0 of 79 patients, p less than 0.0005). All cases of left atrial thrombus or spontaneous contrast were identified in patients with clinically identified cardiac disease. In the 38 patients with no cardiac disease, transesophageal echocardiography identified isolated atrial septal aneurysm and atrial septal aneurysm with a patent foramen ovale more frequently than transthoracic echocardiography (8 versus 2 of 38 patients, p less than 0.05). The two techniques had a similar rate of identifying apical thrombus and mitral valve prolapse. Overall, transesophageal echocardiography identified abnormalities in 39% of patients with no cardiac disease versus 19% for transthoracic echocardiography (p less than 0.005). Thus, transesophageal echocardiography identifies potential cardiac sources of embolism in the majority of patients presenting with unexplained stroke. 