To understand the relationship between branching structure, ventilation distribution, and lung mechanics in health and disease, we have developed a model of coupled parenchymal soft-tissue mechanics and airflow in anatomically-accurate meshes of the lungs and airways. The geometric models are constructed by (1) geometry-fitting a volume mesh¹ to surface data from CT imaging of the lung lobes², (2) fitting centerlines and diameters from the trachea to generations 6-9, and (3) generating airways to fill the lung using a bifurcating-distributive algorithm^3,4. The lung model is surrounded by a surface mesh that represents the pleural cavity, and is filled with a fine mesh of ‘blocks’; each block is associated with a single terminal branch. Mechanics is solved using finite elasticity, with a strain energy function for the compressible lung ‘tissue’. Displacement boundary conditions are applied to the pleural mesh to mimic ventilation. Contact mechanics couples the pleural and lung meshes. For a small displacement, the deformed block volumes are calculated and their changes in volume over time are used as flow boundary conditions for an airflow model in the embedded airway mesh. This predicts terminal node pressures, which are fitted to nodal pressures in the lung mesh. The solutions are iterated, using updated flow boundary conditions and fitted pressures for each solution. Upon convergence, the next incremental deformation is solved. This modeling approach allows analysis of ventilation distribution in response to changes in volume of the pleural cavity, with eventual application in understanding the influence of regional changes in material properties – such as occurs during disease – on the re-distribution of flow. Further extensions to the work will couple the ventilation model to an anatomically-based model of perfusion⁵. Challenges in developing this model include establishing an appropriate material law, accounting for the influence of the airways, and determining methods for validating the model predictions.