Past studies have shown that Trametes versicolor laccase catalyzed Calpha-Cbeta cleavage, Calpha-oxidation. beta-ether cleavage and aromatic ring cleavage of a nonphenolic beta-O-4 lignin model dimer, 1,3-dihydroxy-2-(2,6-dimethoxyphenoxy)-1-(4-ethoxy-3-methoxyphenyl)propane (1), in the presence of 1-hydroxybenzotriazole. In this study, we investigated the detailed degradation mechanism for these pathways of substrate I by laccase/1-hydroxybenzotriazole couple, based on incorporation experiments from (H2O)-O-18 and O-18(2). Oxidation of substrate I in (H2O)-O-18 resulted in the incorporation of O-18 into three aromatic ring cleavage products and a beta-ether cleavage product, These results were identical with those for lignin peroxidase. We infer-red that these cleavages of substrate I proceed via the beta-aryl cation radical intermediate of I. However, the Calpha-Cbeta cleavage degradation product of I by the laccase/1-hydroxybenzotriazole couple was 4-ethoxy-3-methoxybenzoic acid, whereas it was 4-ethoxy-3-methoxybenzaldehyde for lignin peroxidase. It is clear that one atom of O-18 front O-18(2) was incorporated into 4-ethoxy-3-methoxybenzoic acid during the oxidation of substrate I. To confirm the reaction intermediate. we carried out the chemical reaction of 2-(2,6-dimethoxyphenoxy)-1-(4-ethoxy-3-methoxyphenyl)-3-hydroxypropanone with alkaline hydrogen peroxide. since the expected hydroperoxide intermediate is quite similar to that formed from the reaction between the benzylic radical of I and O-2 The result showed that the main degradation product was 4-ethoxy-3-methoxybenzoic acid. Thus, we propose it novel Calpha-Cbeta cleavage via a kind of Baeyer-Villiger reaction for nonphenolic beta-O-4 lignin model dimer by laccase/1-hydroxybenzotriazole couple.