Serum from healthy volunteers contained very little CuZn superoxide dismutase. Larger amounts were found in serum from patients with impaired renal function, and there was a good correlation between serum creatinine and serum CuZn superoxide dismutase content. Almost all superoxide dismutase activity of human serum was cyanide sensitive, and was found to be given by a factor(s) with a molecular mass of approximately 130000. The factor was found in all human extracellular fluids investigated: plasma, serum, lymph, ascites and cerebrospinal fluid. The factor was not recognized by radioimmunoassay for human CuZn superoxide dismutase, and it was not inhibited by rabbit antibodies against human CuZn superoxide dismutase. A similar high-molecular mass factor was found in plasma from all mammals investigated: horse, cow, pig, dog, cat, rabbit, rat and mouse. The activities differed much among species and were mostly higher than those found in human serum/plasma.