The inhalation toxicity of three amorphous silicas (Aerosol 200, Aerosil R 974 and Sipernat 22S) was compared with that of quartz dust. Rast were exposed to 1, 6 or 30 mg Aerosil 200/m3, 30 mg Aerosil R 974/m3, 30 mg Sipernat 22S/m3 or 60 mg quartz/m3 for 6 hr/day, 5 day/wk for 13 wk. Some rats were killed at the end of the exposure period and some were killed 13, 26, 39 or 52 wk after the end of exposure. Clinical signs, body weight, haematology, biochemistry, urinalyses, organ weights, retention of test material in the lungs and regional lymph nodes, collagen content of the lungs, and gross and microscopic pathology were determined in order to disclose possible adverse effects and to study the reversibility, stability or progression of the effects. All test materials induced increases in lung weight, and pulmonary lesions such as accumulation of alveolar macrophages, inflammation, alveolar bronchiolization and fibrosis. In addition, rats exposed to Aerosol 200, Aerosil R 974 or quartz developed granulomatous lesions. Silicosis was observed only in quartz-exposed animals. At the end of the exposure period, Aerosil 200 and quartz had induced the most severe changes. Quartz dust was hardly cleared from the lungs and the changes in the lungs progressed during the post-treatment period, and eventually resulted in lesions resembling silicotic nodules and in one squamous cell carcinoma. Although Aerosil 200 way very quickly cleared from the lungs and regional lymph nodes, the changes in these organs were only partly reversed during the post-exposure period in rats exposed to 30 mg/m3. Aerosil R 974 and the lower levels of Aerosil 200 resulted in less severe, and mostly reversible, changes. The slightest changes were found after exposure to Sipernat 22S, notwithstanding the persistence of this silica in the lungs during the major part of the post-treatment period. The results of this study revealed that only quartz induced progressive lesions in the lungs resembling silicotic nodules. Of the amorphous silicas examined Aerosil 200 induced the most severe changes in the lungs, which only partly recovered, whereas Sipernat 22S induced the least severe, completely reversible lung changes. Chemicals/CAS: Quartz, 14808-60-7; Silicon Dioxide, 7631-86-9