A possible role of melanin precursors in lipid peroxidation was investigated using the lipoxygenase catalysed oxygenation of arachidonic acid (AA) as a model system. Polarographical monitoring of oxygen consumption showed that, among the metabolites examined, 5,6-dihydroxyindole (DHI) was the most active in inhibiting AA oxygenation catalysed by 15-lipoxygenase. The inhibition was found to be concentration-dependent with an IC50 value of 15 microM. Similar effects were observed in the case of the 5-lipoxygenase promoted reaction. Periodical HPLC analysis of the oxidation mixture showed that, in the presence of DHI, the rate of substrate consumption is markedly reduced. The inhibitory potency was significantly increased either by preincubation of DHI with the enzyme or by increasing the time of residence of the indole in aerated buffer solutions prior to contact with the enzyme. Addition of catalase to the incubation mixture resulted in a partial removal of DHI inhibition. From these and other experiments, an inhibition mechanism is proposed which involves inactivation of the enzyme by reactive species, especially hydrogen peroxide, arising from DHI autoxidation.