Proteolytic enzyme activity in sputum was found to be related to the degree of purulency of the specimen and not to reflect any specific disease entity. Protease activity was demonstrated in the respiratory secretions of all patients with cystic fibrosis tested and in the majority of patients with bronchiectasis, but in few of the specimens from patients with other respiratory diseases. The same enzyme was found in eight specimens of pus. The inhibition of proteolysis within purulent sputum by its DNA content is discussed, and a role for DNA in the development of the highly viscous respiratory secretions in cystic fibrosis is postulated.