The effect of reactive co-substrates such as guaiacol and 2,6-dimethoxyphenol on the removal of chlorinated phenols by horseradish peroxidase (HRP) and a laccase from the fungus Trametes versicolor was investigated. Addition of 50 mM guaiacol enhanced the precipitation of 4-chlorophenol, 2,4-dichlorophenol, and 2,4,5-trichlorophenol with peroxidase by 12, 32 and 65%, respectively, and with laccase by 20, 32 and 80%, respectively. Addition of 10 mM 2,6-dimethoxyphenol enhanced the precipitation of 2,4.5-trichlorophenol by 90% with peroxidase and by 98% with laccase. Products from the reaction of 2,6-dimethoxyphenol and peroxidase were filtered to exclude compounds of a molecular weight greater than 500. Incubation of the resulting enzyme-free filtrate with a solution of unreacted 2,4,5-trichlorophenol caused precipitation and a 72% removal of the 2,4,5-trichlorophenol. Chlorophenol precipitation in the presence of co-substrates may be a useful strategy for improving the efficiency of enzymatic decontamination methods, particularly in the case of heterogeneous pollution.