The effect of different parameters (pH, ultrasonic amplitude and pressure) on the resistance to heat and manothermosonication (MTS) treatments of heat resistant lipase and protease produced by Pseudomonas fluorescens B52 and NCDO 2085, respectively, were studied. Lipase B52 thermoresistance decreases with an increase of pH. However, inactivation by MTS seems to be pH independent. There were only slight increases in the MTS efficiency when increasing pressure at UHT temperatures and the effect of amplitude was different depending on treatment temperature. Protease NCDO 2085, which was very resistant to MTS at 30 °C, was very sensitive to MTS at 76 °C. Increases in applied pressure had no effect on MTS efficiency at 140 °C and its inactivation by MTS was almost temperature independent between 76–109 °C. Data obtained are compared with previous published data and inactivation mechanisms are discussed.