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A simple theoretical model based on shear forces generated by the collapse of the ultrasound cavities near the surface of a microorganism is proposed. This model requires two parameters which take into account the number of acoustic cavitation bubbles, and the resistance of the cell wall of the microorganism to the shear forces generated by bubble collapse. To validate the model, high-power low frequency (20 kHz) ultrasound was used to inactivate two microorganisms with very different sizes, viz., a bacterium, Enterobacter aerogenes and a yeast, Aureobasidium pullulans. The inactivation ratio was experimentally measured as a function of sonication time for different ultrasound power and for different initial cell numbers. For both E. aerogenes and A. pullulans the Log of the inactivation ratio decreased linearly with sonication time, and the rate of inactivation increased (D-value decreased) with the increase in …