In recent years, relevant interest has been devoted to activated sludge disintegration and solubilisation techniques in order to cope with the biological limitations related to particulate degradation. Mechanical disintegration with ultrasound can efficiently transform insoluble organics into a soluble form: the solubilised organic matter is released from the cells to the bulk phase, thus accelerating the hydrolysis step in the digestion process. Experiments were carried out on bench scale anaerobic reactors fed with either untreated or disintegrated excess sludge, added with a biomass inoculum taken from a full scale anaerobic digester. Digestion tests have been carried out at different feed/inoculum ratios (F/I) in the range of 0.1–2, kinetics of VS reduction has been investigated and a beneficial effect of sonication is observed for all the experimental conditions. Similar beneficial results have also been found for biogas production with a maximum gain of 25% at 0.5 F/I ratio.