Instillation of respirable glass fibers to rat lungs served as an in vivo model for the detection and evaluation of differential local biological responses to particulate matter in the deep lung. Three compositions of vitreous glass, stonewool. and refractory fiber materials (MMVF 10, HT. and RCF1a) were harvested viith surrounding lung tissues and examined both histologically and by physical/chemical assays to correlate the observed differential dissolution events with specific biological responses associated with each material. Specimens at 2-days. 7-days, 30-days and 90-days post-instillation were compared from at least three rats for each condition and for phosphate-buffered-saline: controls. HT fiber surface and bulk chemistry uniquely allowed direct histochemical visualization of fiber degradation steps by Prussian Blue staining, while multiple attenuated internal reflection infrared spectroscopy and energy-dispersive X-ray analysis of unfixed, fresh lung robe slice surfaces revealed the concurrent biochemical changes, Insulation glass (MMVF 10) dissolved most quickly in extracellular compartments, as well as after phagocytosis of small fragments, stonewool (HT) was externally thinned by surrounding phagocytes and fragmented into shorter lengths engulfable by macrophages; refractory ceramic (RCF1a) resisted both external dissolution and macrophage uptake, becoming embedded in granulomatous nodules. it is clear from these results that the lung can process inadvertently respired particulates in different ways dependent on the specific compositions of the particles. The animal model and analytical scheme reported here also show substantial promise for evaluating the effects of bioaerosols, and synergistic effects of respirable toxins with particulates, and consequences of dental aspirates into the lung.