An insufficient signal-to-noise ratio is a significant limiting factor in assessing intracranial hemodynamic parameters by transcranial Doppler sonography. To establish the feasibility and validity of signal enhancement in transcranial Doppler sonography, stabilized air microbubbles bound to galactose microparticles as a carrier (SHU 454) were used in an animal model. The disadvantage of a short-lasting effect is caused by instability of the contrast medium and a consequent reduced capacity to pass through the lung. Eight pigs received SHU 454 intraarterially in various concentrations and forms of application during transcranial monitoring of the middle cerebral artery with a 2 MHz pulsed ultrasound device. The effect was reproducible, dependent on the dose and application modalities. The best results were obtained with low concentrations (100 mg of microparticles/ml of suspension) and low injection speeds (0.5-1.0 ml/sec) into the common carotid artery by injection pump, reaching a homogeneous average enhancement of 6 to 12 dB over at least 5 minutes. Histological examination of the brain showed no evidence of air embolization. Further development requires a stable solution with similar properties and an ability to pass through the lung, therefore being suitable for intravenous application in humans.