Despite continuing efforts at environmental control, occupational lung disease continues to be a major health problem. Asbestiform and siliceous dusts commonly are implicated as causative factors in fibrotic and carcinogenic pulmonary diseases. The basic pathogenetic mechanisms leading to these conditions are poorly understood and have been approached in a limited fashion. With the increasing availability of electron and X‐ray microanalytical techniques, investigators have been able to determine important associations between inhaled particles and specific anatomic and cellular lesions. In attempts to phagocytize, package, digest, and export particles, pulmonary cells and other functional units put out a variety of proteolytic, elastolytic, and inflammatory products. The alveolar macrophage, as the first line of cellular defense in the lower respiratory tract, plays a major role in mediating the biologic activities of many inhaled particulates. This chapter details electron optical techniques currently used to study the distribution, fate, and biologic activity of inhaled particulates and describes the information available on the mechanisms of particle‐induced lung disease.