Xenon-induced neuroprotection has been well studied both in vivo and in vitro. In this study, the neuroprotective properties of the other noble gases, namely, krypton, argon, neon and helium, were explored in an in vitro model of neuronal injury. Pure neuronal cultures, derived from foetal BALB/c mice cortices, were provoked into injury by oxygen and glucose deprivation (OGD). Cultures were exposed to either nitrogen hypoxia or noble gas hypoxia in balanced salt solution devoid of glucose for 90min. The cultures were allowed to recover in normal culture medium for a further 24h in nitrogen or noble gas. The effect of noble gases on cell reducing ability in the absence of OGD was also investigated. Cell reducing ability was quantified via an MTT assay and expressed as a ratio of the control. The OGD caused a reduction in cell reducing ability to 0.56+/-0.04 of the control in the absence of noble gas (p<0.001). Like xenon (0.92+/-0.10; p<0.001), neuroprotection was afforded by argon (0.71+/-0.05; p<0.01). Neon and krypton did not have a protective effect under our experimental conditions. Helium had a detrimental effect on the cells. In the absence of OGD, krypton reduced the reducing ability of uninjured cells to 0.84+/-0.09 (p<0.01), but argon showed an improvement in reducing ability to 1.15+/-0.11 (p<0.05). Our data suggest that the cheap and widely available noble gas argon may have potential as a neuroprotectant for the future.