Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase form the primary enzymic defense against toxic oxygen reduction metabolites. Such metabolites have been implicated in the damage brought about by ionizing radiation, as well as in the effects of several cytostatic compounds. These enzymes were analyzed in 31 different human normal diploid and neoplastic cell lines and for comparison in 15 normal human tissues. The copper- and zinc-containing superoxide dismutase appeared to be slightly lower in malignant cell lines in general as compared to normal tissues. The content of manganese superoxide dismutase was more variable than the content of the copper- and zinc-containing enzyme. Contrary to what has been suggested before, this enzyme did not appear to be generally lower in malignant cells compared to normal cells. One cell line, of mesothelioma origin (P27), was extremely abundant in manganese-containing superoxide dismutase; the concentration was almost an order of magnitude larger than in the richest normal tissue. Catalase was very variable both among the normal tissues and among the malignant cells, whereas glutathione peroxidase was more evenly distributed. In neither case was a general difference between normal cells and tissues and malignant cells apparent. The myocardial damage brought about by doxorubicin has been linked to toxic oxygen metabolites; particularly, an effect on the glutathione system has been noted. The heart is one of the tissues which have a low concentration of enzymes which protect against hydroperoxides. However, the deviation from other tissues is probably not large enough to provide a full explanation for the high doxorubicin susceptibility. In the present survey, no obvious relationship between generally assumed resistance to ionizing radiation or to radical-producing drugs and cellular content of any of the enzymes could be demonstrated.