The aim of the present study was to assess the effects of the presence and absence of serum in NP suspension media in relation to their cytotoxicity, as well as their potential to cause oxidative stress and stimulate pro-inflammatory cytokine release from J774.A1 murine 'macrophage-like' cells. Different sized (20 nm and 200 nm) carboxylated, fluorescent, model polystyrene beads (PBs) at concentrations from 12.5 mu g m1(-1) to 10014 m1-1 were used. Both 20 nm and 200 nm PBs, independent of the suspension media, were observed to cause limited, yet significant (p < 0.05) cytotoxicity over 48 h up to 10014 m1-1. Significant differences (p > 0.05) were also found between NP size and serum content of the suspension media used. The smaller sized PBs were found to affect intracellular glutathione (GSH) levels, causing a significant loss (p < 0.05) in GSH when suspended in the presence of serum. Subsequent analysis also showed significant (p < 0.05) increases in tumour necrosis factor-a production after 48 h when the 20 nm PBs were suspended in both the presence and absence of serum, compared to the affects observed by the larger, 200 nm sized PBs. In conclusion, the results of the present study show that the interaction of NPs with serum can significantly affect their resultant toxicity in vitro. (C) 2010 Elsevier Ireland Ltd. All rights reserved.