Transcranial duplex real time sonography (TCCS) is a non-invasive imaging modality that allows repetitive examinations of central nervous system vascular and parenchymal anatomy; a broad spectrum of cerebral pathology may be disclosed: vascular changes include ischemic and hemorrhagic stroke, arteriosclerotic vascular degeneration, arteno-venous malformations and aneurysms, as well as neoplastic and degenerative parenchymal disorders. Imaging was performed with a duplex ultrasound system, employing a 2.25 resp. 2.0 MHz phased-array transducer. Imaging was achieved through the acoustic bone window of the temporal bone and through the foramen magnum. For three-dimensional image reconstruction a mechanical position sensor and online video grabbing was applied. To evaluate the potential of a transpulmonary stable ultrasound contrast enhancing agent we used galactose-based SH U 508 A (Levovist, Schering, Berlin) with 1 to 6 i.v. injections per patient in a phase 2/3 clinical protocol. The signal to noise ratio is significantly improved; the Doppler signal intensity is increased by approx. 25 dB. Levovist was well tolerated and no adverse events occurred, approx. 30% of patients had a sensation of heat and slight pain at the injection site during and shortly after the injection. With the increase in signal intensity, the complete circle of Willis, the peripheral arterial branches, the vertebro-basilar system and the basal venous system may be depicted. In addition, tumour parenchyma vascularisation may be detected, as well as improved delineation of arteriovenous malformations and aneurysms. Three dimensional image reconstruction may represent a novel option in contrast enhanced transcranial duplex imaging including additional information about 3D structure and continuity.