The lignin peroxidases (LIP) and manganese peroxidases (MNP) of Phanerochaete chrysosporium catalyze a wide range of lignin depolymerization reactions with lignin models and synthetic lignins in solution. However, their ability to degrade insoluble natural lignin in aqueous media has not been demonstrated. Insoluble isolated poplar lignin similar to natural lignin was treated in vitro in aqueous media for 12 h with LIP, MNP, and both. Treatment with MNP alone slightly increased the solid mass and produced measurable amounts of ligninderived 2,6-dimethoxyhydroquinone and 2-methoxyhydroquinone but did not appreciably decrease the total lignin content. Treatment with LIP alone did not decrease the mass but produced measurable amounts of ligninderived p-hydroxybenzoic acid and slightly decreased the lignin content. Finally, treatment with LIP and MNP together decreased the solid mass by 11%, decreased the lignin content by 5%, and released low-concentration compounds with mass spectra containing the typical lignin-derived electron-impact fragments of mass 107, 137, 151, 167, and 181. These results suggest that MNP increases the effectiveness of LIP-mediated lignin degradation.