Resistance of Staphylococcus aureus mediated by the penicillinase (Pc-ase) plasmid to divalent metal ions of Hg and Cd was found to be controlled by different mechanisms. The Hg resistance of the Pc-ase plasmid-carrying organisms is based upon a process of changing the ion incorporated in the cell into a somewhat innocuous form. This process is independent of temperature and seems to be controlled by an inducible enzyme. The killing effect of Hg salts was not influenced by the coexistence of other di- or monovalent ions such as MgCl(2), CaCl(2), MnCl(2), and NaCl. No vaporization of Hg, which explains the resistance mechanism such as that proposed by Komura et al. for R factor-mediated Hg resistance in enterobacilli, was found in the case of Hg resistance in staphylococci. On the other hand, the resistance to Cd ion is mediated by some protective mechanism to retain the ion outside the cell. Pc-sensitive organisms not carrying the Pc-ase plasmid incorporate Cd ions into the cells, whereas the Pc-ase plasmid-carrying organisms do not. The incorporation of this ion is temperature dependent and does not take place at 4 C. When incubated with this ion at 4 C, Pc-sensitive organisms as well as Pc-resistant organisms are also able to show a resistance. The addition of CaCl(2) could eliminate the killing effect of CdCl(2) with a dose-effective response.