We evaluated the signal-enhancing effect of the novel perfluorobutane-based ultrasound contrast agent BR 14 (Bracco Research, Switzerland) in grey-scale harmonic imaging of the brain parenchyma. Six sedated male beagle dogs were investigated with transcranial grey-scale harmonic imaging (SONOS 5500, 1.8/3.6 MHz). After bolus injection of two different doses of BR 14, acoustic densitometry was performed to quantify changes in regional contrast intensity. In the dogs' brain parenchyma, the mean relative peak increase in acoustic intensity was +61% after administration of 0.05 ml/kg BW of BR 14 and +24% after 0.2 ml/kg BW. In the masticatory muscle, application of the higher dose resulted in a stronger increase in contrast intensity compared to the lower dose. Evaluation of the contralateral base of the skull showed a dose-dependent decrease in acoustic intensity. Bolus injection of BR 14 produces an increase in acoustic intensity, which can be used for the visualization of contrast agent in the brain parenchyma. Using high dosages, a strong signal-enhancing effect in the regions near the ultrasound probe leads to a consecutive attenuation of signals from structures being located beyond ("shadowing-effect"). This is the explanation for the paradoxical result that the higher dose leads to a lower peak signal increase in the brain parenchyma.