Sub-aperture control is provided for high intensity focused ultrasound. Test transmissions are made sequentially from different sub-apertures. The tissue response at the focal regions is determined and used to select sub-apertures. For example, one or more sub-apertures are not used where temperature does not rise above certain threshold or tissue displacement is weak, such as associated with intervening bone or attenuating tissue. Other factors may be used instead or in addition to tissue response at the focal region. Relative proximity of the sub-apertures to a lesion, angular distribution of the sub-apertures, shape or size of the sub-aperture focal regions as compared to the tissue to be treated, or combinations thereof may be used. Once selected, the relative weight for each sub-aperture may be adjusted based on measured tissue response for each sub-aperture, such as to provide more equal treatment contribution from different sub-apertures.