The localization of transforming growth factor beta (TGFB) and insulin like growth factor-I (IGF) in asbestosis were studied using immunohistochemistry. Sheep were instilled intratracheally with 100 milligrams of chrysotile (12001295) asbestos fibers in phosphate buffered saline every 2 weeks for 1 year. Sheep were either maintained with no further exposure (low dose), received 10 milligrams of chrysotile every 10 days (intermediate dose), or received 100 milligrams every 10 days (high dose) for an additional 1 year. Sections of sheep lungs were incubated with polyclonal antibodies to mammalian isoforms of TGFB and IGF. Lung histopathology showed a dose related response. A mild response of increased inflammatory cells was seen in sheep lungs exposed to a low cumulative dose of asbestos; fibrosis and inflammation, alveolitis, and focal honeycombing was seen following intermediate dose; and lungs which had received a high dose showed pathologic changes of increased cellularity, interstitial fibrosis, and focal honeycombing. In unexposed lungs, TGFB antibodies demonstrated the minimal presence of TGF isoforms in bronchial and bronchiolar epithelium, and rare presence in macrophages, cartilage, bronchial and vascular smooth muscle. In exposed lungs, more intense staining was seen in areas of fibrosis and in hyperplastic type-II pneumocytes. Unlike the unexposed lungs, immunostaining showed the presence of TGFB in extracellular matrix zones. IGF immunostaining revealed the presence of the peptides in bronchial and bronchiolar epithelium, bronchial glands, bronchial and vascular smooth muscle, endothelium, and macrophages. In the fibrotic lungs, IGF staining was seen in macrophages and in fibroblasts within and along the border of lesions but, in contrast to TGFB, IGF was not seen in the extracellular matrix. Increased staining was seen in metaplastic proliferating epithelium, fibroblasts, and macrophages in more advanced lesions. The authors conclude that the different localization of TGFB and IGF indicated by immunohistochemistry staining suggests different and complementary roles for the growth factors in asbestosis.