The antagonism between the essential divalent metals calcium and magnesium and the divalent metal carcinogens, lead, nickel and cadmium are under investigation in metabolic and in carcinogenicity studies. A single s.c. injection of cadmium chloride was shown to enhance pancreatic acinar carcinoma formation in male Wistar rats. The inhibition by magnesium acetate of cadmium-induced injection site sarcomas was associated with a decreased accumulation of cadmium at the injection site. Similarly, the injection of magnesium acetate to nickel acetate-treated Strain A mice delayed the accumulation of nickel in the lungs of such animals. Thus, it appears that at least part of the protection afforded by magnesium against the tumorigenic activity of cadmium and nickel is due to diminished accumulation of the carcinogenic metal at the target site. Extension of the possible antagonistic effects of the physiologically essential divalent metals against tumor formation by nickel and lead in other target sites will be explored.