A detailed three-dimensional model of manganese peroxidase was constructed using lignine peroxidase as the structural scaffold. This is the only protein in the peroxidase family except for cytochrome c peroxidase for which a resolved crystal structure is available. The model was built using the following procedure: (a) structurally preserved regions were derived from similar regions in the sequence alignment of the two proteins; (b) non-similar regions were modelled by searching a set of resolved protein structures for fragments which fitted in geometrically and choosing the best fitting fragment. Side chains were constructed by calculating rotamer-rotamer interaction energies and minimizing intramolecular energy. Model refinement was performed by molecular mechanics calculation. The quality of the model was assessed on the basis of the propensity of the amino acids to be inserted into regular secondary-structure elements and to be exposed to solvent. All the lignine peroxidase regions not used for model construction because of the lack of similarity, except the helix fragment Leu261-Phe269, correspond to external loops, suggesting reliable modelling. The manganese peroxidase model structure was analyzed in detail and several functionally relevant structural features were predicted, the most important being: (a) the very close structural similarity between lignine and manganese peroxidase active sites, suggesting a similar mode of hydrogen peroxide activation; (b) the substitution of polar residues for the hydrophobic amino acids exposed at the edge of the channel involved in substrate recognition in lignine peroxidase, suggesting that manganese peroxidase does not directly bind aromatic substrates; (c) the location of residues potentially able to bind Mn2+, spatially positioned on the side of the 3-CH3 heme edge.