Titanium is extensively used for a wide range of implanted medical devices due to its advantageous combination of physico-chemical and biological properties. Nano-size titanium dioxide (TiO2) is also used in a variety of consumer products. Such widespread use and its potential entry through various routes of the body suggest that TiO2 could pose an exposure risk to humans. Nano-size particles (NP) enter systemic circulation, accumulate and damage tissues that are especially sensitive to oxidative stress. We hypothesized that TiO2 NPs can exert diverse cytotoxic effects on various human cell type especially neural cell lines. In order to test our hypothesis, putative cytotoxic effects of oxidative stress due to TiO2 NPs exposure on IM9, U937 and SHSY5Y (human neuroblastoma cells) were investigated in N-acetyl cysteine (NAC), neopterin and dexamethasone pre-treated cell cultures. IM9, U937 and SHSY5Y cells were exposed to ten different concentrations of 25 and 10 nm diameter TiO2 NPs in three different time periods before and after treatment with NAC, neopterin and dexamethasone. To determine toxicity levels of NPs, cell viability was estimated by MTT test. Concentration of cells was assessed by counting trypan blue stained cells with a heamo-cytometer. Toxicity of 25nm TiO2 particles was significantly increased (p < 0.05) by adding fetal bovine serum (FBS) in SHYS5Y and U937 cell lines culture medium. Concentration-dependent toxicity of 10 nm TiO2 NP was weakly increased by adding FBS to SHYS5Y, IM9 and U937 cell culture media. NAC pre-treatment provided significant protection for only SHYS5Y cell exposed to 25 nm and 10 nm of TiO2 NPs after a 24-hour incubation period. Neopterin pre-treated SHYS5Y cells displayed significant increases in viability after 24-hour exposure to 10 nm and 25 nm TiO2 NPs. While exposure of dexamethasone pre-treated U937 cells to 25 nm of TiO2 NPs induced a significant increase in cell survival at only 100 mu g/ml particle concentration, increase in viability of SHYS5Y cells were observed at all concentrations against 10 nm particle challenge. Our study demonstrated that exposure of SHYS5Y to TiO2 NPs for 24 hours regularly induced reduction of cell viability. We also found similar dose-related effects of TiO2 NPs in reducing cell survival in IM9 cells. This study clearly indicated that FBS is an effective dispersing agent for TiO2 NPs and increased TiO2 toxicity in all cell lines. NAC and neopterin significantly protected the SHYS5Y cell against the putative cytotoxic effects of TiO2 NPs.