It is important to consider the interactions of toxic trace elements in an evaluation of the toxicity of environmental pollutants. The in vitro toxicity screening system, using the rabbit alveolar macrophage, provides a particularly useful system for evaluating trace-element interactions since crude particulates containing multiple trace elements can be introduced into the system. Mercury, cadmium, and vanadium are the three most toxic metals that have been tested in the macrophage system. When cells were exposed simultaneously to toxic concentrations of cadmium or mercury and nontoxic concentrations of sodium selenite, the macrophages had significantly higher viability, cell number, and adenosine triphosphate concentration than when they were exposed to the cadmium or mercury salts alone. In analogous experiments, zinc was found to protect against cadmium toxicity, and copper protected the macrophage against the lytic effects of vanadium.