Nanotechnology is an emerging field that demands urgent development of adequate toxicology and risk assessment. The previous experimental data on carbon nanotube respiratory exposure strongly suggest the need for complex evaluation of potential toxicity. Our work demonstrates that after carbon nanotube deposition in the lung, acute local and systemic responses are activated and characterized by a blood gene and protein expression signature. The approach described here will foster the development of biomarkers for application in human screening of nanoparticle exposure.