Lipid peroxidation was induced with porcine retinal homogenates using ferric iron or UV light. A number of lipid and aqueous-soluble antioxidants were tested and their protective effects measured after 60 min of exposure. The iron system produced up to 5 times more lipid hydroperoxides as quantified by the fluorescence thiobarbituric acid (TBA) assay. Of the three substituted dialkyl phenols evaluated, the most efficient was compound S-17224 which was able to afford greater than 90% protection at 10(-4) M concentration in the iron-induced system. At 10(-5) M, inhibition was 78% and at 10(-6) M 33%. By comparison, 10(-4) M gamma-oryzanol inhibited the reaction by 61% and alpha-tocopherol by only 14%. The combination of 10(-6) M S-17224 and 10(-4) M gamma-oryzanol potentiated the effect by another 23%. In the light-catalyzed system. S-17224 and alpha-tocopherol were more efficient (71%). The model system described here is simple and can be employed to study additional antioxidants as well as in the retinotoxic evaluation of ophthalmic drugs.