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The collagen content and its aggregational state was histochemically measured in interstitial lung diseases. Open chest biopsies of ten patients with adult respiratory distress syndrome, seven patients with sarcoidosis, and nine patients with fibrosis associated with connective tissue diseases and with idiopathic pulmonary fibrosis (IPF/CTD) were compared with eight samples of normal lungs. The collagen content of diseased lungs was significantly increased when compared to control lungs, but no difference was observed among the pathologic groups. The analysis of collagen aggregational state showed maximal aggregation in IPF/CTD, followed by sarcoidosis, ARDS, and control lungs, in decreasing order. The results suggest that measurement of collagen aggregation coupled with collagen content could be used in the evaluation of interstitial lung disease and encourage the use of new techniques in order to better explain the dramatic histologic and functional alterations observed in many disease-associated lung processes.