Pulmonary responses in the rat to the inhalation of occupationally applicable levels of silica (14808607) were studied. Specific pathogen free male Fischer-rats were exposed to 2.0mg/m3 silica for 8 hours/day, 5 days per week, for periods of 2 weeks, 2 months, or 6 months. Bronchoalveolar lavage cells were extracted and analyzed for cellular differentials, chemiluminescence, platelet derived growth factor (PDGF), transforming growth factor beta (TGFbeta), and messenger RNA (mRNA) levels of inducible nitric-oxide (NO) synthase (iNOS). Northern analysis revealed mRNA levels for iNOS to be increased after 2 months, but returned to normal at 6 months. An increase in red blood cells and leukocytes revealed pulmonary damage and inflammation after 2 and 6 months of exposure. An increase in total and NO dependent chemiluminescence revealed that oxygen radicals and NO were produced by bronchoalveolar lavage cells after 2 and 6 months. Multiple granulomatous lesions and an increase in collagen synthesis were observed after 6 months, and TGFbeta mRNA levels were also elevated after 6 months; however, PDGF mRNA remained comparable to controls. The authors conclude that the inhalation of silica at concentrations that could occur in the mining and sandblasting industry may present a health concern due to this study's findings that significant pulmonary inflammation and fibrosis occur in rats exposed to occupationally relevant levels of silica.