There is increased use of nanomaterials in many applications due to their unique properties, such as their high surface area and surface reactivity. However, the potential health effects to workers, consumers and the environment exposed to nanoparticles (NPs) is unknown. The aim of this study was to investigate whether NPs which may enter the body could adsorb proteins and whether this interaction affects both the particle and the protein function. The cytokines IL-8 and TNF-alpha were adsorbed significantly more by 14 nm carbon black (CB) compared with a similar dose of 260 nm CB. Uncoated 14 nm CB particles produced a significant increase in intracellular calcium [Ca2+](i) which was greater than a similar mass dose of 260 nm CB. The 260 nm CB produced an increase in ICAM-1 expression in A549 epithelial cells at a comparable dose of 14 nm CB, and after coating with TNF-alpha 260 nm CB produced significantly more ICAM-1 expression compared with control cells. TNF-alpha bound to 14 nm CB induced a level of ICAM-1 expression that was no greater than the control level, suggesting that the TNF-alpha activity may be inhibited. These results suggest that NP-protein interaction results both in a decrease in protein function and particle activity in the cellular assays tested and this is currently being investigated.