The application of ozonation has been limited by the poor mass transfer rate of ozone. In the presence of ultrasonic irradiation, mass transfer of ozone to the liquid phase could be enhanced and hydroxyl radicals may be generated by the decomposition of ozone in the gas phase. This study is to combine ozone with ultrasound (US/O-3) for the removal of tetracycline (TC). The effect of several operational parameters, including gaseous ozone concentration, gas flow rate, hydrogen peroxide concentration, hydroxyl radical scavenger, pH, initial TC concentration and power density on the removal of TC was investigated. The results showed that the TC removal followed pseudo-first-order kinetics. The IC removal rate increased with increasing gaseous ozone concentration, gas flow rate and power density, but decreased with increasing initial TC concentration. The presence of hydrogen peroxide improved the TC removal rate when the hydrogen peroxide concentration was not exceeded 10 mmol L-1. The presence of tert-butyl alcohol inhibited the TC removal rate to some extent. The main intermediates were identified and the degradation pathway of TC was proposed. After 90 min treatment, 91% COD was removed. The acute toxicity of the solution reached the maximum after 10 min treatment and then gradually decreased with the prolonging reaction time. (C) 2011 Elsevier B.V. All rights reserved.