The optimization of ultrasonic irradiation as an advanced oxidation technology can be achieved by adjusting the ultrasonic frequency and saturating gas during sonolysis. The sonolytic production of hydrogen peroxide (H 2 O 2 ) and hydroxyl radical ( • OH) has been investigated at the ultrasonic frequencies of 20, 40, 80, and 500 kHz, respectively, in the presence of four different saturating gases (i.e., Kr, Ar, He, O 2 ) at each frequency. H 2 O 2 was measured with a KI dosimeter, and the formation of • OH was monitored by trapping with terephthalic acid. Both the applied frequency and the physicochemical properties of the saturating gases influence the sonochemical rates of production of • OH and H 2 O 2 . At 20 kHz, the rate contants for the production of H 2 O 2 vary over an order of magnitude as a function of the nature of the dissolved gas (0.0508 and 1.31 µM min -1 ). Similar trends are observed for the production of • OH at the same frequencies and under an identical set of saturating gases. The highest rates of production of H 2 O 2 (pH 7, 2.94 µM min -1 ) and • OH (pH 11, 0.391 µM min -1 ) are observed during sonolysis of Kr-saturated solutions at 500 kHz. Sonolysis of He-saturated solutions at 20 kHz results in the lowest rates of production of H 2 O 2 (0.0508 µM min -1 ) and • OH (0.0310 µM min -1 ). Decreasing differences among the saturating gases at higher frequencies are attributed to changes in bubble dynamics and thermodynamics as the resonant bubble radius decreases from 177 µm at 20 kHz to 7 µm at 500 kHz.