Valproic Acid (VPA) is an antiepileptic drug that is also used now for many other indications, including bipolar and mood disorders. A serious drawback of VPA is that it can induce neural tube defects (NTD) to those exposed in utero. The mechanisms of VPA-induced NTD remain incomplete, but oxidative stress has been implicated. To better understand, the cause of oxidative stress, we measured the activity of superoxide dismutase (SOD) following VPA treatment. SOD is an antioxidant enzyme that when inhibited may also affect the intracellular ROS tone and redox status.P19 cells are embryo carcinoma cells that retain some differentative properties. In cells treated with VPA (5 mM), dichloroflouroscein (DCF) fluorescence as an indicator of ROS production was significantly increased and was similar to ROS generated in cells treated with an SOD inhibitor, LCS-1 (100 µM). In SOD activity assays, VPA caused a decrease (20%) in activity after 6 h. Loss of activity was not due to changes in SOD protein concentrations as immunoblot analysis showed SOD expression to be virtually unchanged with VPA treatment. Also at 6 h of exposure, glutathione redox states (Eh) were highly oxidized as compared to untreated controls. As such, data support that VPA inhibits SOD activity and thereby may serve as a mechanism by which exposure to increases ROS availability and alters intracellular redox states. Understanding these effects may shed some light on embryotoxicity of VPA and its role in NTD pathogenesis.