Hydrogen peroxide-resistant Chinese hamster ovary (CHO) cells displayed cross-resistance to CdCl2, HgCl2 and NaAsO2 but not to Na2Cr2O7, ZnCl2, NiCl2 and CuSO4. Resistance to hydrogen peroxide and to the metals was partially retained by these cells for many generations despite growth in drug-free medium. The loss of resistance was a slow process, and was different for the various metal compounds. Cell variants had a slightly higher content of non-protein intracellular thiols (NPSH) than sensitive cells. This biochemical feature did not seem to be the cause of resistance to CdCl2 but accounted for at least part of the resistance to HgCl2 and NaAsO2. Increased metallothionein synthesis did not seem to be responsible for the metal-resistant phenotype. These results suggest that resistance to specific metal compounds in cultured mammalian cells adapted to hydrogen peroxide is dependent on a number of factors which differ for the various metal compounds and which are characterized by a different stability.