The catalytic activity and selectivity of montmorillonite exchanged with Nat, Fe2+, Co2+, Ni2+ and Cu2+ cations were comparatively investigated in the ozonation of sulfamethoxazole (SMX). Chlorobenzene, benzoic acid, 4-nitrobenzoic acid, 3-hydroxybenzaldehyde, 4-nitrophenol and phenol were used as probe molecules having structural similarity with SMX oxidation intermediates. UV-vis spectrophometry and chemical oxygen demand (COD) measurements showed that Fe(II)-Mt and, to a lesser extent, Co(II)-Mt produce total mineralization of all organic substrates in less than 40 min. Combined HPLC-mass spectrometry revealed a reverse proportionality between the degradation time and molecular size of the organic substrates. Oxalic acid was recognized as a common bottleneck in the ozonation of any organic substrates. Ozonation initially obeyed a first order kinetics, but adsorption took place after 3-5 min, inducing changes in the mechanisms pathways. These findings may be useful for tailoring optimum oxidative treatment of waters without accumulation of hazardous derivatives. (C) 2015 Elsevier B.V. All rights reserved.