The prevalence of a right-to-left intracardiac shunt, demonstrated by echocardiography and transcranial Doppler sonography has been shown to be higher in stroke patients than in normal controls. The aim of this study was to assess the sensitivity and specificity of contrast transcranial Doppler sonography in comparison to transesophageal echocardiography in the detection and differentiation of intracardiac and intrapulmonary shunts and to correlate the transcranial Doppler findings with clinical outcome and morphological findings. Forty five consecutive stroke patients with suspected paradoxical embolism were entered into the study. In all 25 patients with middle cerebral artery stroke of the left (56%) or right (44%) territory and echocardiographic demonstrated patent foramen ovale (80%) or intrapulmonary shunt (20%), simultaneous bilateral transcranial Doppler sonography of the middle cerebral arteries was performed after contrast medium injection during rest and valsalva straining under standardized and optimized conditions. Overall sensitivity for the detection of a right-to-left shunt by contrast transcranial Doppler sonography was 97% and overall specificity was 70%. Bilateral appearance of microbubbles, microbubble count and time delay of microbubble appearance significantly increased after valsalva straining. In patients with intracardiac shunts, a significantly higher microbubble count (32 vs. 13 in patients with an intrapulmonary shunt) and a shorter time interval of microbubble appearance (11 vs. 14 s in patients with intrapulmonary shunts) was observed. There was no correlation between the side and numerical distribution of microbubble count and the location and severity of the current clinical symptoms, as well as between microbubble count and presence and hemispherical distribution of brain infarcts. Transcranial Doppler sonography is a highly sensitive method for the detection of right-to-left shunts, whether of cardiac or pulmonary location. However. no correlation was found between the side and number of microbubbles counted and the clinical symptomatology.