To assess the feasibility and usefulness of contrast-enhanced sonography for tumor detection and guidance of liver VX2 tumor ablation and to evaluate post radiofrequency ablation effectiveness. VX2 tumors were implanted into the livers of 6 rabbits. Both conventional and harmonic gray scale and power Doppler imaging were performed with a commercially available scanner to evaluate the liver tumors before and after intravenous injection of a sonographic contrast agent before and after radiofrequency ablation. Contrast-enhanced imaging was used to detect the tumors before ablation, to guide needle insertion, and to measure the ablation sites after radiofrequency ablation. Pathologic examination was performed for comparison. Three tumors were seen without contrast enhancement, whereas 10 tumors (<1 cm) were detected with contrast enhancement. Intentionally, 2 tumors were completely ablated and 5 tumors were partially ablated. In 3 cases, incompletely ablated tumors could only be identified on contrast-enhanced Doppler imaging by enhancing the detection of residual tumor vascularity. There was excellent concordance between sonographic imaging and gross pathologic findings. Contrast-enhanced sonographic imaging appears useful for detection of liver tumors and for guiding and monitoring tumor ablation therapies.