Negative-pressure casting techniques have been used for obtaining silicone rubber casts of the avian respiratory system, which contains minute air capillaries, noncompressible hollow bones, and highly flexible air sacs. The possibilities of this technique for the study of human airway diseases, which present technical difficulties similar to those of avian lungs, are investigated here. Left lungs from patients with various obstructive lung diseases or with normal lungs were fixed at autopsy under 25 cm H₂O airway pressure with 2.5% phosphate-buffered glutaraldehyde. Cannulated, isolated lobes were placed in a vacuum chamber, and Dow Corning 734 RTV silicone elastomer, diluted with 10% low viscosity silicone oil, was introduced into the airways at -10 kPa. Following complete polymerization, the tissue was microdissected to reveal the lung cast in situ, and histological sections were obtained for correlative studies. The tissue was then macerated in 5.25% sodium hypochlorite. The total time from fixation to finished cast was 3-4 days. Linear shrinkage of the elastomer was less than 1% in glutaraldehyde or water and between 1 and 2% in bleach. The negative-pressure injection technique enabled complete and accurate filling of airways to the alveolar duct level at physiological pressures and provided good delineation of blind cavities such as obstructed airways or ectatic mucous gland ducts. The technique proved useful for the study of obstructive lung disease and should also prove useful for modelling aerosol deposition in diseased lungs.