The ozonation of six microcystins (MCs) (MC-LR, MC-RR, MC-LA, MC-LF, MC-YR, and MC-LW) was investigated with a focus on the kinetics and decrease in toxicity. Second-order rate constants for the reactions of the six MCs with O₃ and •OH (k_O3,MC and k•OH,MC) ranged from 7.1 × 105 to 6.1 × 106 M^–1 s^–1 (kO3,MC) and from 1.2 × 1010 to 1.8 × 1010 M^–1 s^–1 (k•OH,MC), at pH 7.2 and 20 °C. The activation energies were calculated to be 21.6–34.5 and 11.6–13.1 kJ mol^–1 for kO3,MC and k•OH,MC, respectively. The rate constants did not show an important pH dependency, except for kO3,MC-YR, which increased at pH > 7. A kinetic model using the determined rate constants and the measured exposures of O₃ and •OH was able to precisely predict the removal of MCs in natural water. The hepatotoxicities of MCs were decreased by ozonation; the toxicities of the four MCs (MC-LR, MC-RR, MC-LA, and MC-LF) decreased nearly concurrently with decreases in their concentrations. However, MC-YR and MC-LW showed a gap between the concentration and toxicity as a result of the incomplete destruction of the Adda moiety (a key amino acid expressing the hepatotoxicity of MCs). A product study using liquid chromatography–mass spectrometry identified a number of oxidation products with an intact Adda moiety produced by the ozonation of MC-YR and MC-LW.