The relationship between particle characteristics and in vitro toxicity was investigated using Chinese hamster ovary cells. Test dusts included respirable natural (Nat) and flux-calcined (FC) diatomaceous earth (DE), quartz, cristobalite, TiO2, and chrysotile and crocidolite asbestos. All dusts elicited a qualitatively similar, concentration-dependent response: particle uptake, induction of micro- and polynuclei, and reduction in cell proliferation. However, similar mass concentrations of the dusts yielded a 35-fold range of toxicity: chrysotile > crocidolite>Nat DE>FC DE>quartz>Cristobalite>TiO2. In vitro toxicity did not correlate with crystalline silica content, surface area, composition, volume, particles/cm2, or fibrous geometry. Toxicity was closely associated with the number of particles/cm2culture surface that had at least one dimension > 7.5 µm. Thus particle size but not shape could be a determinant of in vitro toxicity. Particle size might also impact in vivo pathogenesis.