The effect of trace metals on plasma alpha1-antitrypsin was studied in vitro by adding known concentrations of trace metals, either alone orin combination, to plasma. Cadmium was the only trace metal that reduced the concentration of alpha1-antitrypsin and depressed the trypsin inhibitory capacity. No such effects were found with divalent lead, mercury, nickel, iron, and zinc ions. The present study appears to offer a plausible explanation for the emphysema that occurs in industrial workers exposed to cadmium.