Purpose: To evaluate if Pulse Inversion Harmonic Imaging with contrast agent injection (Levovist) is able to determine an increase of echogenicity in normal hepatic parenchyma, and to compare its capability to detect metastatic focal lesions with that of standard US and spiral CT. To define and standardize the technical and methodological aspects of this new technique., Material and Methods: A selected group of 72 patients (42 males and 30 females) with clinical and instrumental suspect of hepatic metastatic lesions was included in the prospective study. Each patient was examined by conventional ultrasound (US), Pulse Inversion Harmonic Imaging (PI) and spiral-CT (spCT). US examination was performed using an HDI 5000 (ATL, Bothell, USA) equipped with a broadband probe (5.0-2.0 MHz). 2.5 g Levovist (Schering AG-Berlin) was administered intravenously, at concentration of 300 mg/ml and a flow rate of 7 ml/min. Video clips obtained with the acquired images before and after contrast medium administration were transferred to a magnet optic disk unit. Examinations were evaluated by an experienced radiologist blindly on a workstation that allowed a qualitative-quantitative analysis. SpCT images were evaluated separately by another experienced radiologist. US images were evaluated qualitatively (number of lesions, site of lesion, diameter of the smallest lesion detectable) and quantitatively (increase in parenchymal echogenicity 20", 40", 60" and 5' after the injection of contrast agent)., Results: In all cases examined, the echogenicity of normal hepatic parenchyma increased after contrast agent administration, reaching a peak of about 250% (1DS) at 60 s and a decreasing gradually in 5 minutes. Conventional US detected 195 focal lesions, CT 231, and US with pulse inversion technique and contrast agent (US-PI) 287. Mean differences among the number of lesions detected by the different techniques per each patient were also calculated. Wilcoxon Signed Rank Test showed a statistically significant difference between US-PI and US (p < .0001), CT and US (p = .0052) and US-PI and CT (p = .0121). US-PI detected the smallest lesions, which went undetected by the CT and conventional US examinations., Discussion and Conclusions: In 10 cases (14.3%) contrast enhanced US-PI demonstrated the presence of a number of lesions greater than 5 (diffuse metastatization and inoperability) in comparison to that detected by spCT). The greater echogenicity of normal hepatic parenchyma using pulse inversion technique after Levovist infusion allowed to better demonstrate hepatic metastases. This technique showed a higher identification rate of small lesions in comparison to basal examination and to spiral CT. Contrast enhanced US-PI demonstrated a remarkable increase in echogenicity of hepatic parenchyma in portal phase. The technique significantly improves the detection of focal lesions allowing visualization of smaller lesions compared to CT and US. These results indicate that the technique could be used in the staging of liver metastasis. However, large multicentric trials are required to validate US-PI and better define its role in the work-up of patients with neoplastic disorder.