The objective of this study was to evaluate mechanisms of the synergy between high intensity-focused ultrasound (HIFU) and docetaxel and to determine the best sequence of chemotherapy administration in relation to HIFU treatment for obtaining optimum control of tumoral growth. A total of 15 days after s.c. implantation of the tumor, 52 Copenhagen rats studied were randomized in 4 groups of 13: controls, docetaxel alone (group 1), HIFU and docetaxel concomitant (group 2) and HIFU and docetaxel administered 24 h before treatment (group 3). The number of HIFU shots was calculated in order to cover 75% of the tumor volume. The effects of docetaxel, HIFU and their interaction on tumor volumes were analyzed using a linear regression. The distributions of the tumor volumes were significantly greater in the control group than in the group 1 (P = 0.002) and than in both groups 2 and 3 (P<0.0001 and P = 0.0001). These volumes were also significantly greater in group 1 than in both groups 2 and 3 and there was no difference between the groups 2 and 3. The tumor doubling times were 7.8 days for the group 1, 43.8 days for the group 2, 16.1 days for the group 3 and 5.9 days for the controls. The mechanism of the synergy between HIFU and docetaxel on the growth of Dunning tumors is apparently multifaceted. The results are encouraging because in the two groups of rats treated with the combination of HIFU and docetaxel, the percentage of complete remission was approximately 30%.