Oxidative stress in human amyloid deposits from patients with systemic amyloidosis, such as familial amyloidotic polyneuropathy (FAP), primary amyloidosis, and secondary amyloidosis, was examined immunohistochemically by means of an affinity purified anti-hydroxynonenal (HNE) antibody to HNE, a marker of lipid peroxidation. Furthermore, the levels of thiobarbituric acid reactive substances (TBARS), which is another marker of lipid peroxidation, and the levels of protein carbonyl, a maker of protein modifications by free radicals, were determined in FAP patients and healthy controls. Affinity purified anti-HNE antibody reacted with amyloid deposits in all types of amyloid tissues examined. Significantly higher levels of TBARS and protein carbonyl were found in amyloid rich tissues of FAP patients compared with those in the control subjects. These results verify that lipid peroxidation via free radical injury occurs in amyloid deposits in systemic amyloidosis. The protein modifying properties of free radicals increase the likelihood that they play an important role in the amyloid formation process.