We propose that the brain monoamine metabolism is one of the protective systems against oxidant- and free radical-induced damage in brain. In the present study, we show that norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) protect brain homogenate and mitochondria against iron-dependent lipid peroxidation and protect brain microsomes against both iron-dependent and iron-independent lipid peroxidation. These compounds protect deoxyribose and benzoate against free radical-induced degradation and aromatic hydroxylation. Electron spin resonance studies show that the monoamines are excellent scavengers or inhibitors of 1,1-diphenyl-2-picryl hydrazyl radicals in organic solution, of superoxide and hydroxyl radicals in aqueous solution, and of carbon-centered radicals induced by iron ions in brain homogenate. Pro-oxidant properties were found in Fe(II)-H2O2-induced glutamic acid and 2-aminobutyric acid degradation, and confirmed in Fe(III)-bleomycin-dependent DNA degradation in a biphasic manner. The above effects are approximately in the order of NE = DA = 5-HT; DA > DOPAC > HVA; and 5-HT > 5-HIAA. Related supportive and contrary observations and hypotheses are discussed. Attempts are also made to briefly interpret some experimental and clinical observations.