Freshly prepared, aqueous solutions of cigarette smoke suppressed the elastase-inhibitory capacity of human serum. Immunoelectrophoresis of mixtures of aqueous smoke solution, human serum, and pancreatic elastase showed decreased elastase/alpha1-proteinase inhibitor complexes and increased free, active protease. Phenolic antioxidants prevented the suppression of serum elastase-inhibition by cigarette smoke. By contrast, treatment of serum with model oxidants caused a similar suppression of elastase inhibition. These results suggested that emphysema in cigarette smokers might be due, in part, to the local suppression of alpha1-proteinase inhibitor in lung by oxidizing agents present in cigarette smoke.