Rats were exposed by inhalation to 5 or 50 mg/m3 Mount St. Helens volcanic ash, to 50 mg/m3 quartz (positive controls), or to filtered room air (sham-exposed controls), for 6 hr/day, 5 days/week, for up to 24 months to investigate biological effects of chronic inhalation exposure to volcanic ash under controlled laboratory conditions. Exposure-related lung changes comprised accelerated respiratory frequency; alveolar macrophage accumulation; interstitial reaction; lymphoreticular reaction in peribronchiolar regions and in mediastinal lymph nodes; alveolar proteinosis in the 50- mg/m3 ash- or quartz-exposed groups; increase in fresh lung weights; decreased body weight and increased mortality in the quartz-exposed group; and epidermoid carcinomas especially in the quartz-exposed females and, to a lesser extent, in the 50-mg/m3 ash-exposed females. The observed changes reflect significant dose-response and agent-response relationships.