Abstract Connective tissue ground substance forms a substantial portion of lung tissue and may be implicated in the development of pulmonary emphysema and fibrosis. Hexosamine, an important constituent of ground substance, and its components, galactosamine and glucosamine, were determined in lung tissue from laboratory animals of varying ages and human necropsy material. Each specimen was graded histologically. Correlations were made with the clinical course and autopsy material. The mean pulmonary hexosamine content in healthy animals of several species extended from 0.771 to 0.583 mg. per 100 mg. of tissue dry weight and averaged 0.652 mg. for normal human lung. The mean ratio of galactosamine to glucosamine ranged from 0.19 at age 2 months to 0.16 for 2-year-old rabbits, and averaged 0.223 in man. Variation within a species proved to be small, and the absence of significant change throughout a broad life span of laboratory animals suggested that age-dependent hexosamine alterations were unlikely in lung tissue. Fifteen specimens, characterized histologically as pulmonary emphysema, averaged 0.671 mg. per cent for hexosamine content and 0.249 for the galactosamine-glucosamine ratio, compared to means of 0.782 and 0.170, respectively, for 18 specimens exhibiting the microscopic findings of acute infection, hemorrhage, or edema. These studies demonstrated that galactosamine-glucosamine ratios were considerably higher than control values in certain emphysema specimens, although group differences were not significant statistically. In the presence of acute histologic change, however, the mean hexosamine content increased, and the average galactosamine-glucosamine ratio decreased. These differences were statistically significant. It is suggested that these hexosamine changes may have been associated with basic alterations in lung ground substance that could contribute to the development of chronic pulmonary disease. An alternative explanation is that the bioochemical findings reflected differences in pulmonary blood content.