The anticonvulsant lamotrigine and atypical antipsychotic olanzapine, as therapeutic alternative mood stabilizing drugs to lithium and valproate, are well-tolerated maintenance treatments for bipolar disorder. Previous studies in our laboratory showed that both lithium and valproate increased expression of glutathione s-transferase (GST)-M1 subtype in primary cultured rat cerebral cortical cells. GST conjugates glutathione, the major antioxidant in brain, with a variety of oxidized products to form non-toxic and excretable products, and plays an important role in cellular protection against oxidative stress. The purpose of the present study is to determine whether lamotrigine and olanzapine also regulate GST-M1. Using immunoblotting analysis and spectrophotometric assay, we examined the effect of lamotrigine or olanzapine on GST-M1 protein levels and GST enzyme activity in primary cultured rat cerebral cortical cells. We found that chronic treatment with lamotrigine or olanzapine increased both GST-M1 protein levels and GST enzyme activity. These results suggest that GST-M1 may contribute a significant component to the treatment of bipolar disorder with mood stabilizing drugs.