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Adult C57BL\/6 mice were exposed via single intratracheal instillations to free forms of TiO<jats:sub>2<\/jats:sub>NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO<jats:sub>2<\/jats:sub>NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO<jats:sub>2<\/jats:sub>NPs were characterized for size, surface area, chemical impurities, and agglomeration state in the exposure medium. Pulmonary transcriptional profiles were generated using microarrays from tissues collected one and 28 d postexposure. Property\u2010specific pathway effects were identified. Pulmonary protein levels of specific inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (<jats:italic>P<\/jats:italic> \u2264 0.05; fold change \u2265 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO<jats:sub>2<\/jats:sub>NPs clustered mainly by postexposure timepoint followed by particle type. A pathway\u2010based meta\u2010analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO<jats:sub>2<\/jats:sub>NP gene expression response. Embedding of TiO<jats:sub>2<\/jats:sub>NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary inflammation differed across all particles; however, the underlying pathway perturbations leading to inflammation were similar, suggesting a generalized mechanism\u2010of\u2010action for all TiO<jats:sub>2<\/jats:sub>NPs. Thus, transcriptional profiling is an effective tool to determine the property\u2010specific biological\/toxicity responses induced by nanomaterials. Environ. Mol. 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