Inhalation of asbestos fibers and silica crystals causes debilitating lung disease in humans. We have established animal models to study several basic pathogenetic mechanisms. For asbestos, rats were exposed to an aerosol of chrysotile fibers for one hour. Inhaled fibers were deposited initially on alveolar duct bifurcations. Five hours after initial deposition, significant numbers of asbestos fibers were cleared from alveolar surfaces. These fibers were translocated to alveolar macrophages, to alveolar epithelial cells, as well as to basement membranes, interstitial cells and connective tissue. One day after exposure, asbestos laden macrophages significantly increased tissue volume in the region of alveolar duct bifurcations where the asbestos originally was deposited, thus forming the initial lesions of asbestosis. Similarly, the number of aerosolized crystalline silica particles on alveolar surfaces was significantly reduced 6 hrs after exposure, and by 24 hrs post-exposure, alveolar particles were rare. Silica h and by 24 hrs post-exposure, alveolar particles were rare. Silica had been translocated to macrophages and epithelial cells. Interestingly, 65% of the macrophages lavaged from the lungs of exposed animals contained silica crystals by six hours post-exposure. This percentage was maintained through a 24-day post-exposure period, but the number of intracellular particles decreased over time.