The disposition of sodium valproate in pregnant rats was studied comparing with nonpregnant (control) rats. In the pregnant rats, the total plasma clearance decreased significantly (p<0.05) from 7.06 ml/min/kg of the control to 5.34 ml/min/kg, whereas the plasma elimination half-life of valproate did not change. The serum unbound fraction (f_s) of pregnant rats increased remarkably. The f_s of the fetal plasma was lower than that of the maternal serum in spite of the lower albumin (main binding protein for valproate) concentration in the fetal plasma. A non-linear serum (plasma) protein binding was observed both in the control and the fetal rats, but not observed in the pregnant rats. In the pregnant rats, the tissue-to-plasma concentration ratio (K_p) of the brain was higher than that in the control rats, whereas the K_p values of the liver and lung were lower than those in the control rats. In other tissues, the K_p values did not show a significant difference. Rapid placental transfer was observed and the K_p value of the fetus was 0.43.