Ultrasonic irradiation is a promising technique for the degradation of persistent organic molecules such as pharmaceuticals in wastewater. This paper focuses on the sonolytic degradation of ciprofloxacin (CIP), a fluoroquinolone antibiotic. During a first experiment at 25°C and 544kHz, the degradation of a 15mgL −1 CIP-solution showed a pseudo-first order degradation constant k 1 equal to 0.0067±0.0001min −1 (n=3). Experiments with the addition of t-butanol as a radical scavenger showed that reaction with OH radicals is the main degradation route for ciprofloxacin. Since the production of OH radicals was the highest at 544kHz, this was also the most favorable frequency for CIP degradation in comparison with 801 (k 1 =0.0055min −1 ) and 1081kHz (k 1 =0.0018min −1 ). The degradation constant is also strongly dependent on the temperature of the bulk solution. The degradation constant increased significantly with increasing temperature from 0.0055min −1 at 15°C to 0.0105min −1 at 45°C. According to the Arrhenius law, the apparent activation energy was determined to be 17.5kJmol −1 . This suggests that the degradation of CIP is diffusion controlled, as is the case for most radical reactions. A Langmuir-type heterogeneous reaction kinetics model could be used to explain the increasing degradation constant with decreasing initial CIP concentration from 0.0204min −1 (C 0 =0.15mgL −1 ) to 0.0009min −1 (C 0 =150mgL −1 ). According to the model a local reaction zone exists at the interface region of the cavitation bubbles. During bubble oscillation, molecules accumulate in the reaction zone and when the bubble finally collapses, the molecules in the reaction zone can be oxidized by the formed OH radicals. This means that degradation is limited by the available surface at the interface. The model agreed very well with the experimental data (R 2 =0.975). The pseudo rate constant for decomposition (k d ) was estimated to be 0.40μMmin −1 and the modeled equilibrium constant (K) was equal to 0.047μM −1 .