We have engineered novel hemoproteins with high catalytic activity by introducing several hydrophilic residues in the axial ligand of microsomal cytochrome b(5), an electron transfer protein. Some (H39S and H39Q) of these mutants possess quite high peroxidase-like reactivity as designed. One (H39C) of them shows very low catalytic reactivity, and this may be attributed to the unique hexa-coordination (His-Fe3+-CyS) for this mutant.