High-Intensity Focused Ultrasound (HIFU) can produce radical tissue necrosis. We wanted to assess tumor destruction, proliferation, and tumorigenesis after HIFU, in an animal model of hepatic tumor. New Zealand rabbits bearing VX-2 solitary liver tumors were treated with extracorporeal HIFU under ultrasound (US) guidance and standardized conditions. Groups differed only for the administration of either one or two consecutive HIFU procedures. Tissue destruction was assessed by stereomicroscopy and planimetry, cell proliferation was estimated by in viuo intra-arterial injection of 1200 pCi [3H]thymidine, and tumorigenesis was tested by reimplantation of treated or untreated pieces of liver tumors into the thighs of nontumor-bearing animals. Mortality was 0. Tumor destruction rates were 76.3% 2 1670 after one procedure and 94.2% ? 7.3% after two procedures. Nuclear staining was heavy in control tumors and was absent in treated tumors. Untreated hepatic tumors induced measurable tumors at 3 weeks in thighs of all recipients, 7.8 -t 2.4 cm3 in volume. Hepatic tumors treated with one HIFU procedure induced tumors in the thigh of recipients in 31.3% of cases (0.47 2 0.06 cm3), and those treated with two HIFU procedures induced tumors in 0% even after 8 weeks of follow-up. In conclusion, HIFU allows a noninvasive approach to the destruction of liver tumors in this model, with little toxicity but significant effects on proliferation and tumorigenesis. The repetition of HIFU procedures may improve results. (HEPATOLOGY 1995;21:832-836.) Surgery is considered the best treatment for liver tumors. Until now, only surgical resection has proven beneficial to survival in patients bearing colorectal metastases,' and such is probably the case for liver transplantation in selected patients with small hepatocellular carcinomas.2 However, surgery presents short-Abbreviations: HIFU, high-intensity focused ultrasound; US, ultrasound.