Sera from 354 patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of reactive nitrogen intermediates, antinuclear antibodies and the anti-oxidase copper-thionein (Cu-thionein), and compared to sera from healthy donors and patients with non-rheumatic diseases including AIDS, various internal as well as neurological diseases and carcinoma of different organs. When compared to healthy individuals, the levels of nitric oxides in sera from patients with autoimmune rheumatic diseases were elevated by 240-600% (P < 0.01). The status of reactive nitrogen intermediates (NOx, RNI) in sera from donors with inflammatory rheumatic diseases was increased by 170-540%, but was also significantly enhanced in sera of patients with non-rheumatic diseases, indicating a general inflammatory mechanism that is predominantly triggered by inducible nitric oxide (NO) syntheses of phagocytes. All rheumatic sera were dramatically depleted of the anti-oxidase Cu-thionein (P < 0.001), a powerful consumer of hydroxyl radicals and singlet oxygen and an efficient superoxide dismutase. The NOx levels were positively correlated with the serum titers of antinuclear antibodies (r = 0.77) and negatively correlated with Cu-thionein levels (r = 0.94), reflecting a high steady-state concentration of free radicals generated during inflammatory and autoimmune rheumatic diseases.