Inflammatory responses following exposure of carbon nanoparticles to human macrophage and endothelial cells were employed as indicators of particulate biological activity. Hundred nanometer carbon particles (nC) with and without nonextractable surface-bound iron were synthesized using a templating approach, and human monocyte-derived macrophages (MDM) were exposed to various concentrations of these particulates. Supernatants recovered from MDM 24 h postexposure were assayed for the inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) by a quantitative ELISA and tested for their ability to induce expression of intercellular adhesion molecule-1 (ICAM-1) on human endothelial cells (EC) by immunofluorescence flow cytometry. Data generated by these experiments demonstrated that nC-Fe was far more biologically active than nC. In addition, the chemical reactivity of nC-Fe toward decomposition of hydrogen peroxide to form hydroxyl radicals was significantly higher than that of nC and correlated well with the increase in the strength of the inflammatory response, though a direct proof of creation of hydroxyl radicals in the biological system is not provided. Comparison with micrometer-sized carbon and carbon-iron particles suggests that the chemical and biological reactivity is correlated with surface area.