A method for tracking the 3-D motion of tissues in real-time is combined with a 2-D high-intensity focused ultrasound (US), or HIFU, multichannel system to correct for respiratory motion during HIFU therapy. Motion estimation is based on an accurate ultrasonic speckle-tracking method. A pulse-echo sequence is performed for a subset of the transducers of the phased array. For each of these subapertures, the displacement is estimated by computing the 1-D cross-correlation of the backscattered signals acquired at two different times. The 3-D motion vector is then computed by a triangulation algorithm. This technique is experimentally validated in phantoms moving as fast as 40 mm s(-1), and combined with HIFU sequences. A real-time feedback correction of the HIFU beam is achieved by adjusting the delays of each channel. The sonications "locked on target" are interleaved with very short motion-estimation sequences. Finally, in vitro experiments of "locked on target" HIFU therapy are performed in fresh moving tissues.