and CBZ, may possibly enhance the transformations of AEDs into epoxide, which may result in increased AED teratogenesis. On the other hand, the effects of AEDs on the detoxification or elimination process of epoxide have not yet been fully clarified. Our study clearly showed that therapeutic concentrations of VPA show inhibitory effects on the activities of EH and most of the GST isozymes, and that these effects are concentration dependent. Therapeutic concentrations of CBZ also inhibited the activity of GST 7-7, found primarly in the placenta. These results suggest that detoxification of the epoxide of AEDs could be inhibited under AED polytherapy by using VPA or CBZ or both. This may partly explain the increased incidence of malformations in offspring exposed to VPA-CBZ, administered with or without other AEDs. PHT, PB, and ZNS had no inhibitory effects on the activities of EH and GST. However, the possibility that PHT and PB have inducing effects on epoxide formation should be taken into account. In this regard, combinations of AEDs should be carefully selected in the treatment of women of childbearing age with epilepsy. (This work was supported by Grant-in-aid No. 05454309 for Scientific Research from the Ministry of Education and Culture and grant from the Hirosaki Research Institute for Neurosciences.)