Synthetic aperture focusing using a virtual source was used previously to increase the penetration and to extend the depth of focus in high-frequency ultrasonic imaging. However, the performance of synthetic aperture focusing is limited by its high sidelobes. In this paper, an adaptive weighting technique based on a focusing-quality index is introduced to suppress the sidelobes. The focusing-quality index is derived from the spatial spectrum of the scan-line data along the mechanical scan direction (i.e., the synthetic aperture direction) after focusing delays relative to the virtual source have been applied. The proposed technique is of particular value in high-frequency ultrasound in which dynamic focusing using array transducers is not yet possible. Experimental ultrasound data from a 50-MHz imaging system with a single-crystal transducer (f-number = 2) are used to demonstrate the efficacy of the proposed technique on both wire targets and speckle-generating objects. An in vivo experiment also is performed on a mouse to further demonstrate the effectiveness. Both 50-MHz fundamental imaging and 50-MHz tissue harmonic imaging are tested. The results clearly demonstrate the effectiveness in sidelobe reduction and background-noise suppression for both imaging modes. The principles, experimental results, and implementation issues of the new technique are described in this paper.