Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell-dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m(3) had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.