BACKGROUND: The present investigation was undertaken to evaluate the neuroprotective effect of etomidate against N-methyl-D- aspartate (NMDA) induced neurotoxicity in rat cortical neurons by measuring lactate dehydrogenase (LDH). METHODS: The cerebral cortical neurons of fetal rat were grown for 12 days in dissociated cell culture. They were divided into four groups: first group acted as control with no drug administration and other groups treated with either NMDA 100microM or Etomidate (ET) 10microM + NMDA 100microM or ET 100microM + NMDA 100microM After 24 hrs, cell death was assessed by morphology under the light microscope and quantified by measuring the LDH in the culture media. RESULTS: In the light microscopic findings, the intact cortical neurons were increased in the ET groups. NMDA-induced LDH production also significantly suppressed in ET group (P<0.05). There were no significant difference between the ET 10microM and 100microM groups. CONCLUSIONS: These results suggest that the etomidate has protective effect on the cultured rat cortical neurons against NMDA-induced neurotoxicity.