PURPOSE To assess contrast material-enhanced harmonic power Doppler and fundamental color Doppler ultrasonography (US) in the detection of residual viable tumor tissue after radio-frequency (RF) ablation in tumors embedded in fat. MATERIALS AND METHODS Twenty-eight VX2 tumors were implanted into the retroperitoneum of 14 rabbits. Tumors were examined with contrast-enhanced fundamental color Doppler US and harmonic power Doppler US before and 10 minutes after RF ablation. Saline-enhanced RF ablation (30 mL/h) was performed over 10 minutes with 28-W RF power. Follow-up included repeat US examinations. Necropsies and histopathologic assessment were performed after detection of residual untreated tumor at US or 3 weeks after ablation. RESULTS VX2 tumors reached a mean size of 21 mm +/- 9 (SD) (size range, 6-43 mm) 25 days after implantation. All tumors larger than 31 mm showed signs of central necrosis at US. Before ablation, intense vascularity was detected in all tumors with both contrast-enhanced US modes. Histopathologic assessment at the end of the follow-up period revealed local relapses due to incomplete ablation in 14 (50%) of 28 cases. Detection of residual tumor was missed in all cases with contrast-enhanced color Doppler US. Contrast-enhanced harmonic power Doppler US depicted residual flow in 12 of the 14 cases (sensitivity, 86%) in which local relapses occurred. There was a significant (P <.005, McNemar test) improvement in detection of residual tumor when the harmonic power Doppler mode was used. CONCLUSION Contrast-enhanced harmonic power Doppler US has greater sensitivity than contrast-enhanced color Doppler US for detecting residual VX2 tumor following ablation. Therefore, contrast-enhanced harmonic power Doppler US may be a useful additional method for the detection of residual tumors after RF ablation.