1. The comparative protective abilities of zinc L-methionine, zinc DL-methionine, zinc sulfate, zinc gluconate, L-methionine, DL-methionine, and vitamin E succinate (VES) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation, DNA fragmentation, and glutathione depletion in the hepatic and brain tissues, and production of reactive oxygen species by peritoneal macrophages were assessed. In addition, mice were fed a zinc-deficient diet for 5 weeks, and treated with TPA and/or zinc L-methionine or zinc DL-methionine, and similar studies were conducted. 2. The zinc-deficient diet induced oxidative stress in the hepatic and brain tissues as well as in the peritoneal macrophages as evidenced by significantly enhanced lipid peroxidation. DNA fragmentation, glutathione depletion, and production of reactive oxygen species. 3. Treatment of mice with zinc L-methionine, zinc DL-methionine, and VES decreased TPA-induced reactive oxygen species production as evidenced by significant decreases in chemiluminescence in peritoneal macrophages by approximately 45%, 31%, and 47%, respectively, and cytochrome c reduction by approximately 54%, 35%, and 41%, respectively, as compared with control values. Similar results were observed with liver and brain lipid peroxidation, DNA fragmentation, and glutathione depletion. 4. Zinc salts and antioxidants provided significant protection against TPA-induced oxidative damage. Zinc L-methionine provided the best protection.