Background/Aims: Diagnosis of hepatocellular carcinoma (HCC) relies strongly on the detection of hypervascularity in the arterial phase and, in this setting, spiral computed tomography (CT) is the most widely used method. This prospective study aimed to investigate the usefulness of low mechanical index harmonic ultrasound (US), using a second generation contrast-enhanced technique, in the assessment of vascular pattern of HCC shown to be hypervascular at spiral CT. Methods: A total of 79 cirrhotic patients with 103 nodules (mean +/- SD 28 +/- 13 mm) with arterial hypervascularity at spiral CT were studied. US examination was performed by perfusional sonography, using a new dedicated technology (CnTI-Esaote(TM)), operating at low mechanical index, after injection of a second generation contrast agent (SonoVue(TM)-Bracco), allowing detection of tumoral flow during arterial phase. Results: Selective arterial enhancement on perfusional sonography was observed in 94/103 nodules (91.3%), with a sensitivity of 66.6, 87.5, 91.7, and 97.3% in nodules less than or equal to 1 cm, > 1 less than or equal to 2 cm, > 2 less than or equal to 3 cm, and > 3 cm respectively. Conclusions: Perfusional sonography shows good diagnostic agreement with spiral CT in hypervascular HCC and may be proposed for the immediate vascular characterization of nodules detected at US and used as second imaging technique to confirm hypervascularity in cirrhotic nodules. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.