Lignin peroxidase (LIP) catalyzed oxidation of 4-bromophenol (4-BP) resulted in the formation of dimers as evidenced by GC-MS analysis. However, 4-BP was considered a poor substrate, since it exhibited a high K-m value of 600.9 muM and during oxidation, LIP was subjected not only to H2O2 but also product-dependent inactivation. Oxidation was enhanced by inclusion of gelatin, which suppressed product-dependent inactivation and by inclusion of the dimethoxylated non-phenols, veratrole (VO) and 3,4-dimethoxycinnamic acid (DMCA) which mediated 4-BP oxidation. The mediation role of VO and DMCA is attributed to their oxidation potential (OP) values in the aqueous phase (6.04 eV for VO and 6.03 eV for DMCA), which implies that once oxidized to their respective cation radicals, they preferentially oxidize substrates of lower OP (5.12 eV for 4-BP phenolate ion). Inclusion of the mediators enabled complete 4-BP oxidation at high H2O2 concentrations, overcoming H2O2-dependent inactivation, When the reactive ferulic acid (FA) was included as a co-substrate, its oxidation preceded that of 4-BP, and since LIP was inactivated in the process, no oxidation of 4-BP was noticed. In the case of horseradish peroxidase (HRP), 4-BP oxidation was enhanced by inclusion of FA, even though oxidation of the latter preceded that of 4-BP. Additional studies indicated that this resulted from interaction of FA-oxidation products with 4-BP, In the presence of caffeic acid and catechol, reduced oxidation of 4-BP was evident for both enzymes. In the presence of syringaldehyde, concomitant oxidation was evident for both enzymes, resulting in enhanced oxidation by HRP and moderate-to-slight enhancement by LIP.