We investigated the effect on cell death of reactive oxygen species induced by water-soluble cationic metalloporphyrins with superoxide dismutase (SOD) activity. The SOD activity of 5,10,15,20-tetrakis(4-N-methylpyridyl)]porphine (MPy₄P) containing Fe, Mn or Cu was measured using a cytochrome c assay by the xanthine/xanthine oxidase system and stopped-flow kinetic analysis. Cell viability of four cell lines treated with metalloporphyrins, mitomycin c (MMC), or cisplatin was estimated by a trypan blue exclusion assay. FeMPy₄P with a high SOD activity showed a significant cytotoxicity compared with MMC and cisplatin, while CuMPy₄P without SOD activity exhibited no cytotoxicity. However, MnMPy₄P showing an SOD activity as high as that of FeMPy₄P did not indicate cytotoxicity. These findings suggest that FeMPy₄P as SOD mimic converts intracellular O₂^⋅− to H₂O₂ and that it rapidly reacts with H₂O₂ to form ^⋅OH, causing DNA damage and inducing cell death. On the other hand, MnMPy₄P did not participate in the Fenton reaction, so that DNA damage in the cells treated with MnMPy₄P was not observed. In addition, the cytotoxicity by the metalloporphyrin was inversely correlated with the SOD activity of the cells and the selective damage at cellular and DNA levels was confirmed. We believe that for an anticancer drug with antioxidant ability O₂^⋅− is useful as a target molecule to induce selective cell death between cancer and normal cells and that metalloporphyrins showing SOD activity and Fenton-like reaction are a new class of anticancer agents.