This work aims at investigating for the first time the key sonication (US) parameters: power density (DUS), intensity (IUS), and frequency (FS) - down to audible range, under varied hydrostatic pressure (Ph) and low temperature isothermal conditions (to avoid any thermal effect). The selected application was activated sludge disintegration, a major industrial US process. For a rational approach all comparisons were made at same specific energy input (ES, US energy per solid weight) which is also the relevant economic criterion. The decoupling of power density and intensity was obtained by either changing the sludge volume or most often by changing probe diameter, all other characteristics being unchanged. Comprehensive results were obtained by varying the hydrostatic pressure at given power density and intensity. In all cases marked maxima of sludge disintegration appeared at optimum pressures, which values increased at increasing power intensity and density. Such optimum was expected due to opposite effects of increasing hydrostatic pressure: higher cavitation threshold then smaller and fewer bubbles, but higher temperature and pressure at the end of collapse. In addition the first attempt to lower US frequency down to audible range was very successful: at any operation condition (DUS, IUS, Ph, sludge concentration and type) higher sludge disintegration was obtained at 12 kHz than at 20 kHz. The same values of optimum pressure were observed at 12 and 20 kHz. At same energy consumption the best conditions - obtained at 12 kHz, maximum power density 720 W/L and 3.25 bar - provided about 100% improvement with respect to usual conditions (1 bar, 20 kHz). Important energy savings and equipment size reduction may then be expected.