Interactions between Cd and other metal ions are important from both nutritional and toxicological aspects. As Cd is toxic to isolated hepatocytes, these cells can be used to investigate the effects of other metals on Cd-induced cellular injury. Isolated hepatocytes were incubated at 37 degrees C with vehicle (saline); Cd (200 or 400 microM); or Cd plus Cr, Mn, Zn, Ni, Pb, Se, or Fe (200-1000 microM). Evidence of cellular injury was assessed by loss of intracellular K+ and aspartate aminotransferase from the hepatocytes. Effects on lipid peroxidation, as measured by concentration of the thiobarbituric acid reactants, were assessed. Uptake of 109Cd and interaction of the other metal ions with this accumulation were also quantitated. Cell injury due to Cd was consistently reduced by Cr, Mn, Zn, Pb, and Fe. Lipid peroxidation due to Cd was inhibited by Cr, Mn, and Zn. All the metals except Ni produced an increase in the amount of Cd accumulated by hepatocytes. There was no consistent relation between reduction of cellular toxicity and either inhibition of lipid peroxidation or uptake of Cd. These experiments show that (1) protective properties of some metals seen in vivo can be demonstrated at the cellular level and (2) protective effects of metals in general on Cd-induced cellular toxicity are not due to a decrease in either Cd uptake or lipid peroxidation.