The author concludes from a study of the literature that the ground substance of lung parenchyma might play a fundamental role in the development of pulmonary emphysema. This ground substance forms part of the connective tissue and consists predominantly of acid mucopolysaccharides (AMPS) and of acid mucopolysaccharide-protein ‘ complexes (AMPS-PC). Changes in composition of this ground substance may lead to a loss of viscosity and to a diminution of the cohesive properties in the fiber skeleton of the lung parenchyma. Analysis of pieces of fresh lung tissue removed during thoracic surgery (published in detail elsewhere in this issue) revealed a significant difference in AMPS composition between normal and emphysematous tissue, and the difference is compatible with a loss of viscosity in the emphysematous lungs. Practically all mechanisms proposed as being involved in the pathogenesis of lung emphysema can be thought of as acting through a change in composition and viscosity of the ground substance. This gives a universal character to the hypothesis formulated. The fact that emphysema is far more frequent in the masculine sex can also be explained by this hypothesis. The author hopes that his observations may contribute to an insight into the pathogenesis of lung emphysema and may perhaps lead to a more efficacious and functional treatment in early cases.