Homogenates of guinea pig lung show significant protease activity at pH values from 2.2 to 9.9. Perfusion results in increased activity in both acid and alkaline ranges. Protease activity can be extracted by repeated homogenization and sonication of the pellet. Some of the neutral and alkaline proteases require a dialyzable co-factor and are inhibited by 1.2 mM Ag+and Cu++. 2-mercaptoethanol increases activity of the acid cathepsins and of an enzyme at pH 9.9, while DFP inhibits at both acid and alkaline pH. Lung is very active as shown by the „profile“ of its total protease activity over a wide pH range. Serum can inhibit protease activity of lung extracts through the whole pH range tested.