The two silicon dioxide polymorphs, quartz and cristobalite, are known to have different toxicities. The clearance kinetics and biological response of two sources of quartz and one source of pure cristobalite were compared. Models were also developed to show the accumulation of cristobalite in the lungs of Fischer 344 rats as the result of short-term exposures at three different concentrations. The amount of cristobalite cleared from the lung was considerably less than that of the two quartz materials, with little or no clearance after the initial 30 days post exposure. As an indicator of the cellular biological response to the aerosols, total and differential cell counts were measured on bronchoalveolar lavage specimens. Cristobalite showed an early and sustained response with an elevated macrophage, neutrophil, and lymphocyte count through 180 days post exposure. The two quartz materials were not identical in their biological behavior even though they had identical crystal structure and similar trace element analysis. One quartz sample (MIN5) showed an increase in cell response (macrophage, neutrophils, and lymphocytes) approximately 30% that of cristobalite, whereas the other quartz material was not significantly different from control values. In addition, lung hydroxyproline content was greater in the cristobalite-exposed animals.