Brief inhalation exposure of rats to three or six puffs of cigarette smoke significantly decreases elastase inhibitory capacity per milligram of alpha 1-antitrypsin in lung lavage fluid. This effect is not observed in ozone-tolerant rats and can be reversed by treating the lung lavage fluid from smoke-exposed rats with reducing agents. Samples of human serum obtained immediately after smoking also show decreased elastase inhibitory capacity per milligram of alpha 1-antitrypsin. Again, elastase inhibitory capacity can be restored by treatment with a reducing agent. Cigarette smoking may cause emphysema by inactivating alpha 1-antitrypsin through oxidation.