Non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as dizocilpine (MK-801) produce schizophrenia-like psychosis in humans and induce the expression of heat shock protein 70 (HSP70) in rats. The present study examines the effects of antipsychotic drugs, haloperidol and risperidone, on the expression of HSP70 produced by MK-801 in rat C6 glioma cells. After pretreating with haloperidol and risperidone for 1 h, 6 h, 24 h and 72 h, respectively, C6 glioma cells were cultivated again in MK-801 for 6 h, and then, the extent of HSP70 expression was measured by immunoblotting using anti-HSP70 monoclonal antibody. The expression of HSP70 induced by MK-801 significantly decreased as the duration of haloperidol pretreatment was extended (p = 0.002). Risperidone also increasingly attenuated the expression of HSP70 produced by MK-801 as the duration of pretreatment grew longer (p = 0.003). The present findings show that haloperidol and risperidone decrease the HSP70 expression in MK-801-treated rat C6 glioma cells. These results suggest that HSP70 and NMDA receptors may play a significant role in the pathophysiology of schizophrenia.